Nebulizing catheter system and methods of use and manufacture

ABSTRACT

A method and apparatus for delivering a medicine to a patient via the patient&#39;s respiratory system with control and efficiency. A nebulization catheter is positioned in the patient&#39;s respiratory system so that a distal end of the nebulization catheter is in the respiratory system and a proximal end is outside the body. In a first aspect, the nebulization catheter may be used in conjunction with an endotracheal tube and preferably is removable from the endotracheal tube. The nebulization catheter conveys medicine in liquid form to the distal end at which location the medicine is nebulized by a pressurized gas or other nebulizing mechanism. The nebulized medicine is conveyed to the patient&#39;s lungs by the patient&#39;s respiration which may be assisted by a ventilator. By producing the aerosol of the liquid medicine at a location inside the patient&#39;s respiratory system, the nebulizing catheter provides for increased efficiency and control of the dosage of medicine being delivered. In further aspects of the nebulizing catheter apparatus and method, alternative tip constructions, flow pulsation patterns, centering devices, sensing devices, and aspiration features afford greater efficiency and control of aerosolized medicine dosage delivery.

This is a continuation of application Ser. No. 08/261,866, filed Jun.17, 1994; now abandoned.

REFERENCE TO RELATED APPLICATION

The present application incorporates by reference the copendingapplication entitled "IMPROVED CATHETER SYSTEM FOR DELIVERY OFAEROSOLIZED MEDICINE FOR USE WITH PRESSURIZED PROPELLANT CANISTER" filedby the same inventor of the present application and on even dateherewith.

BACKGROUND OF THE INVENTION

The present invention relates to aerosol delivery of medication to thelungs and more particularly, the present invention relates to deliverysystems for application of nebulized medication to the lungs withimproved delivery rates, efficiencies, and control.

Many types of medication can be administered to a patient via therespiratory tract. Medication delivered through the respiratory tractmay be carried with a patient's inhalation breath as airborne particles(e.g. an aerosol or nebula) into the lungs where the medication cancross through the thin membrane of the alveoli and enter the patient'sbloodstream. Delivery of medication via the respiratory tract may bepreferred in many circumstances because medication delivered this wayenters the bloodstream very rapidly. Delivery of medication to the lungsmay also be preferred when the medication is used in a treatment of adisease or condition affecting the lungs in order to apply or target themedication as close as physically possible to the diseased area.

Although delivery of medication via the respiratory tract has been usedfor many years, there are difficulties associated with prior systemsthat have limited their use and application. For example, conventionalmethods have provided for only limited medication delivery rates,efficiency, and control. Conventional methods for aerosol deliveryresult in a substantial portion of the medicine failing to be deliveredto the lungs, and thereby possibly being wasted, or possibly beingdelivered to other parts of the body, e.g. the trachea.

Aerosols in general are relatively short-lived and can settle out intolarger particles or droplets relatively quickly. Aerosols can alsoimpact each other or other objects, settle out as sediment, diffuse, orcoalesce. Aerosol particles can also be subject to hydroscopic growth asthey travel. Delivery of medicine as airborne particles requiresconversion of the medicine, which may be in liquid form, to an aerosolfollowed relatively quickly by application of the aerosol to therespiratory tract. One such device that has been utilized for thispurpose is an inhaler. Inhalers may atomize a liquid to form an aerosolwhich a person inhales via the mouth or nose. Inhalers typically provideonly limited delivery of medication to the lungs since most of themedication is deposited on the linings of the respiratory tract. It isestimated that as little as 10-15% of an aerosol inhaled in this wayreaches the alveoli.

Aerosol delivery of a medication to a patient's respiratory tract alsomay be performed while the patient is intubated, i.e. when anendotracheal tube is positioned in the patient's trachea to assist inbreathing. When an endotracheal tube is positioned in a patient, aproximal end of the endotracheal tube may be connected to a mechanicalventilator and the distal end is located in the trachea. An aerosol maybe added to the airflow in the ventilator circuit of the endotrachealtube and carried by the patient's inhalation to the lungs. A significantamount of the aerosolized medication may be deposited inside theendotracheal tube and the delivery rate of the medicine to the lungsalso remains relatively low and unpredictable.

The low and unpredictable delivery rates of prior aerosol deliverysystems have limited the types of medications that are delivered via therespiratory tract. For new medications that are relatively expensive,the amount of wasted medicine may be a significant cost factor in theprice of the therapy. Therefore, it would be advantageous to increasethe delivery rate or efficiency of a medicine delivered to the lungs.

Another consideration is that some aerosols delivered to the lungs mayhave adverse side effects, e.g. radioactive tracers used for lung scans.Therefore, it would be advantageous to minimize the overall amount ofmedication delivered while maintaining the efficacy of the medication byproviding the same or a greater amount of the medication to the desiredsite in the respiratory tract.

Further, some medications may be more effective when delivered incertain particle sizes. Accordingly, an improved aerosol delivery systemmay provide for improved rates and efficiencies of delivery also takinginto account the aerosol particle size.

It may also be important to administer certain medications in specific,controlled dosages. The prior methods of aerosol delivery not only wereinefficient, but also did not provide a reliable means to controlprecisely the dosage being delivered.

It may also be advantageous to be able to target medication to aspecific bronchus, or specific groups of bronchia, as desired, whileavoiding delivery of medication to other portions of the lungs.

Taking into account these and other considerations, aerosol delivery viathe respiratory tract could become an even more widely used andeffective means of medication delivery if the delivery rate andefficiency of the delivery could be improved.

SUMMARY OF THE INVENTION

According to an aspect of the present invention, there is provided amethod and apparatus for delivering a drug with control and efficiencyto a patient via the patient's respiratory system. A nebulizationcatheter is positioned in the patient's respiratory system so that adistal end of the nebulization catheter is in the respiratory system anda proximal end is outside the body. According to a first aspect, thenebulization catheter may be used in conjunction with an endotrachealtube and preferably is removable from the endotracheal tube. Thenebulization catheter conveys medicine in liquid form to the distal endat which location the medicine is nebulized by a pressurized gas orother nebulizing agent. The nebulized medicine is conveyed to thepatient's lungs by the patient's respiration which may be assisted by aventilator. The nebulizing catheter incorporates alternativeconstructions taking into account anatomical considerations and theproperties of the medicine being nebulized to provide delivery ofmedicine with control and efficiency.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an exploded view of a first embodiment of the presentinvention.

FIG. 2 shows an assembled view of the embodiment of FIG. 1.

FIG. 2A is a sectional view of the nebulization catheter of FIGS. 1 and2.

FIG. 3 is a plan view of an alternative embodiment of the endotrachealtube shown in FIGS. 1 and 2.

FIG. 4 is a cross sectional view taken along the line a-a' of thealternative embodiment of the endotracheal tube shown in FIG. 3 withoutthe nebulizing catheter in place.

FIG. 5 is a cross sectional view taken along the line b-b' of thealternative embodiment of the endotracheal tube shown in FIG. 3 with thenebulizing catheter in place.

FIG. 6 is a plan view of an embodiment of the nebulizing catheter ofFIGS. 1 and 2 shown in place in the trachea of a patient who is notintubated.

FIG. 7 is a view similar to that of FIG. 6 showing an alternativeembodiment of the nebulization catheter.

FIG. 8 is a cross section taken along lines a-a' of the nebulizationcatheter of FIG. 7.

FIG. 9 is a view similar to that of FIG. 7 showing an alternativeembodiment of the nebulizing catheter shown in FIG. 7.

FIG. 10 is a perspective view of a distal end of an alternativeembodiment of the nebulization catheter shown in FIG. 1.

FIG. 11 is a perspective view of a distal end of an alternativeembodiment of the nebulization catheter shown in FIG. 1.

FIG. 12 is a perspective view of an alternative embodiment of FIG. 11with the liquid lumen shown in a closed condition.

FIG. 13 is a perspective view of the embodiment of FIG. 12 with theliquid lumen shown in an open condition.

FIG. 14 is a perspective view of a distal end of an alternativeembodiment of the nebulization catheter shown in FIG. 1.

FIG. 15 is a perspective view of a distal end of an alternativeembodiment of the nebulization catheter shown in FIG. 1.

FIG. 16 is a perspective view of a distal end of an alternativeembodiment of the nebulization catheter shown in FIG. 1.

FIG. 17 is a perspective view of a distal end of an alternativeembodiment of the nebulization catheter shown in FIG. 10.

FIG. 18 is a perspective view of a distal end of an alternativeembodiment of the nebulization catheter shown in FIG. 1.

FIG. 19 is a sectional view of the distal end of the embodiment of thenebulization catheter shown in FIG. 18.

FIG. 20 is a sectional view of a distal end of an alternative embodimentof the nebulization catheter shown in FIG. 1.

FIG. 21 is a sectional view similar to that of FIG. 20 showing analternative embodiment of the nebulization catheter shown in FIG. 20.

FIG. 22 is a perspective view partially in section of a distal end of analternative embodiment of the nebulization catheter shown in FIG. 1.

FIG. 23 is a view similar to that of FIG. 22, showing an alternativeembodiment of the nebulization catheter shown in FIG. 22.

FIG. 24 is a perspective view partially in section of a distal end of analternative embodiment of the nebulization catheter shown in FIG. 1.

FIG. 25 is sectional view of a distal end of an alternative embodimentof the nebulization catheter shown in FIG. 25.

FIG. 26 is sectional view similar to that of FIG. 25 showing theembodiment of FIG. 25 during an exhalation stage of the patient.

FIG. 27 is a perspective view of alternative embodiments of thenebulization catheter and endotracheal tube shown in FIG. 1.

FIG. 28 is a perspective view of alternative embodiments of thenebulization catheter and endotracheal tube shown in FIG. 27.

FIG. 29 is a perspective view of an alternative embodiment of thenebulization catheter shown in FIGS. 27 and 28.

FIG. 30 is a perspective view of the embodiment of the nebulizationcatheter shown in FIG. 29 shown with an endotracheal tube in a patient'strachea.

FIG. 31 is sectional view of a distal end and a diagrammatic view of aproximal end of an alternative embodiment of the nebulization cathetershown in FIG. 1.

FIG. 32 is a cross section view of the embodiment of the nebulizationcatheter shown in FIG. 31 taken along the line a-a'.

FIG. 33 is sectional view of a distal end of an alternative embodimentof the nebulization catheter shown in FIG. 1.

FIG. 34 is sectional perspective view of a distal end of an alternativeembodiment of the nebulization catheter and endotracheal tube shown inFIG. 2.

FIG. 35 is sectional view of a distal end of an alternative embodimentof the nebulization catheter shown in FIG. 1.

FIG. 37 is a cross section view of the embodiment of the nebulizationcatheter shown in FIG. 36 taken along the line a-a'.

FIG. 38 is a perspective view of a distal end of an alternativeembodiment of the nebulization catheter shown in FIGS. 36 and 37.

FIG. 39 is a perspective view of alternative embodiments of thenebulization catheter and endotracheal tube shown in FIGS. 37 and 38.

FIG. 40 is sectional perspective view of a distal end of an alternativeembodiment of the nebulization catheter shown in FIG. 1.

FIG. 41 is a perspective view of alternative embodiments of thenebulization catheter and endotracheal tube of FIG. 1 shown in apatient's trachea.

FIG. 42 is a side view of an another embodiment of the nebulizationcatheter of FIG. 1 showing an alternative centering device.

FIG. 43 is a side view of an another embodiment of the nebulizationcatheter of FIG. 1 showing another alternative centering device.

FIG. 44 is a side view of an another embodiment of the nebulizationcatheter of FIG. 1 showing yet another alternative centering device.

FIG. 45 is a side view of the embodiment of FIG. 44 shown in anotherstage of operation.

FIG. 46 is a side view of a distal end of a nebulization catheterpositioned in a patient's trachea illustrating an undesirable condition.

FIG. 47 is a perspective view similar to that of FIG. 40 of alternativeembodiments of the nebulization catheter and endotracheal addressing thecondition shown in FIG. 46.

FIG. 48 shows an alternative embodiment of the nebulizing catheter andendotracheal tube of FIG. 47 positioned in a patient's trachea.

FIG. 49 shows an alternative embodiment of the nebulizing catheter ofFIG. 6.

FIG. 50 is a diagram illustrating an embodiment of a drug reservoir andpressurization assembly that can be utilized in connection with theembodiment of the nebulization catheter of FIG. 1.

FIG. 51 is a diagram similar to that of FIG. 50 illustrating analternative embodiment of the drug reservoir and pressurizationassembly.

FIG. 52 is a sectional view along line c-c' of FIG. 51.

FIG. 53 is a side view of an alternative embodiment of FIG. 1 includingan optional humidification and heating arrangement.

FIG. 54 is a side view of a flow control system used in connection withthe embodiment of FIG. 1 used for pressuring the liquid flow lumen.

FIG. 55 is a view similar to that of FIG. 54 showing the flow controlsystem of FIG. 54 in another stage of operation.

FIG. 56 is a perspective view of an alternative embodiment of thepresent invention illustrating an alternative method of use.

FIG. 57 is a perspective view illustrating an entire nebulizationcatheter system including sensors.

FIG. 58 shows a sectional view of an embodiment of a nebulizing catheterincluding a sensor.

FIG. 59 shows an alternative embodiment of the nebulizing catheter shownin FIG. 58.

FIG. 60 is a sectional view of a distal end of an alternative embodimentof the nebulizing catheter of FIG. 1.

FIG. 61 is a sectional view of an embodiment of the present inventionthat incorporates a baffle to generate a secondary aerosol.

FIG. 62 is a sectional view of another embodiment of the presentinvention that incorporates a baffle to generate a secondary aerosol.

FIG. 63 is a sectional view of yet another embodiment of the presentinvention that incorporates a baffle to generate a secondary aerosol.

FIG. 64 is a sectional view of still another embodiment of the presentinvention that incorporates a baffle to generate a secondary aerosol.

FIG. 65 is a diagram illustrating an embodiment of the present inventionthat incorporates a pressurized drug/propellant mixture canister.

FIG. 66 is a side view of an embodiment of a nebulizing catheterincorporated into of a suction catheter.

FIG. 67 is a detailed sectional view of the tip portion of the suctioncatheter--nebulizing catheter embodiment of FIG. 66.

FIG. 68 is a perspective view of the embodiment of FIG. 66 positioned inan endotracheal tube in a patient's respiratory system.

FIG. 69 is cross sectional view of the embodiment of FIG. 66 taken alonglines a-a'.

FIG. 70 is a perspective view similar to FIG. 68 showing the suctioncatheter advanced during an further stage of operation.

FIG. 71 is a side view of a proximal end of an endotracheal tubeillustrating an arrangement of receiving a suction catheter and anebulization catheter into the endotracheal tube.

FIG. 72 is an alternative embodiment of the arrangement shown in FIG.71.

FIG. 73 is another alternative embodiment of the arrangement shown inFIG. 71.

FIG. 74 is another embodiment of a suction catheter incorporatingaerosol delivery by nebulization.

FIG. 75 is still another embodiment of a suction catheter incorporatingaerosol delivery by nebulization.

FIG. 76 is a sectional view of a distal end of an embodiment of anebulizing catheter also incorporating a vibrating tip.

FIG. 77 is a sectional view of another embodiment of the nebulizingcatheter incorporating micropulsation of the liquid supply.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

The present invention provides for the controlled and efficient deliveryof an aerosolized medication to the lungs of a patient by nebulizationof a medication at a distal end of a catheter positioned in therespiratory tract. Throughout this specification and these claims, thenebulization catheter is described as used for the delivery of medicineor medication. It is intended that the terms "medication", "medicine",and "drug" should be understood to include other agents that can bedelivered to the lungs for diagnostic or therapeutic purposes, such astracers, or for humidification.

I. Nebulizing Catheter--Basic Configuration

Referring to FIGS. 1 and 2, there is depicted a first embodiment of thepresent invention. FIGS. 1 and 2 show an endotracheal tube 10 which maybe a conventional endotracheal tube. The endotracheal tube 10 may havean inflatable cuff 12 located close to its distal end to facilitatepositioning the tube 10 in the patient's trachea, or alternatively theendotracheal tube 10 may be of a type without an inflatable cuff. Theinflatable cuff 12 is connected via a separate inflation lumen in theendotracheal tube 10 to a proximal fitting 13 for connection to a sourceof inflating gas (not shown). The endotracheal tube 10 has a proximalend connected to a manifold fitting 14. The fitting 14 has a port 15suitably adapted for connection to a ventilator circuit (not shown). Thefitting 14 also includes another port 16 that permits the introductionof a separate catheter into the endotracheal tube from the proximal end.The fitting 14 may be similar in construction to the elbow fittingdescribed in U.S. Pat. No. 5,078,131 (Foley), the entire disclosure ofwhich is incorporated herein by reference. In FIG. 1, a nebulizingcatheter 20 is located in a position ready to be inserted into aventilation lumen 22 of the endotracheal tube 10 via the proximalfitting 14. In FIG. 2, the nebulizing catheter 20 is positioned fully inthe endotracheal tube 10 with a proximal end extending out of the port16 of the proximal fitting 14.

At a proximal end of the nebulizing catheter 20 is a manifold 24. Themanifold 24 includes at least a gas port 28 and a liquid (medicine) port32. These ports 28 and 32 may include conventional attaching means, suchas luer lock type fittings. In addition, these ports 28 and 32 may alsoinclude closure caps 31 that may be used to close the ports when not inuse and may be popped open when connection to a gas source or a liquidsource is desired. optionally, the manifold 24 may also include a filterlocated in-line with either the gas port 28 or the liquid port 32 orboth ports to prevent lumen blockages by particulate matter. Thenebulization catheter 20 includes at least two separate lumens (as shownin FIG. 2A). A first lumen 33 is used for conveyance of a liquidmedicine and communicates with the port 32 on the manifold 24. The otherlumen 34 is used for conveyance of a pressurized gas and communicateswith the port 28 on the manifold 24. The liquid lumen 33 communicateswith a distal liquid orifice 35 and the gas lumen 34 communicates with adistal gas orifice 36 near a distal end 37 of the nebulization catheter20. The distal opening 36 of the pressurized gas lumen 34 directspressurized gas across the distal liquid lumen opening 35 therebynebulizing the liquid medication so that it can be delivered to thepatient's lungs. The distal liquid orifice 35 may be open or may beprovided with a porous material plug or a sponge-like or felt-likematerial plug which may extend slightly from the distal orifice and thatallows liquid to flow from the orifice yet reduces the likelihood ofliquid drooling from the tip.

The length of the nebulization catheter 20 should be sufficient so thatthe distal end 37 can be located in the desired location in therespiratory system while the proximal end (i.e., including the manifold24) is accessible to the physician or other medical personnel forconnection to suitable gas and liquid supplies external of the patient'sbody. Accordingly, the length of the nebulization catheter is dependentupon the size of the patient in which it is being used. A shorternebulization catheter may be preferred in smaller patients, such asinfants or children, and a longer nebulization catheter may be neededfor adults. For example, a nebulization catheter suitable for adults mayhave a length of approximately 45 cm. In one embodiment, approximately30 cm of the nebulizing catheter 20 is in the endotracheal tube 10. Thenebulization catheter may be introduced into the respiratory systemthrough a patient's mouth or via a tracheostomy tube or through thenasal passages. The nebulization catheter may also be used to deliver anaerosol to a patient's nasal passages in which case the length may becorrespondingly shorter.

As explained in more detail below, the generation of an aerosol plumewith the desired geometry, particle size, velocity, etc., requires thatthe distal gas and liquid orifices have small dimensions. Also asexplained below, the distal gas orifice 36 and the distal liquid orifice35 should be in close proximity to each other in order to produce anaerosol with the desired characteristics and efficiency. Further, inorder to provide the desired medicine delivery rates and to operate withreasonably available pressure sources, the liquid and gas lumens in thenebulizing catheter should be as large as possible, consistent withanatomical requirements. Accordingly, the nebulization catheter 20 has amultiple stage construction with a larger shaft size and larger lumensin a main shaft section and a smaller shaft size and smaller lumens in adistal shaft section.

As shown in FIG. 2A, the nebulizing catheter 20 is composed of a shaft38 having a main section 39 and a distal section 40. In the main shaftsection 39 of the nebulization catheter, the liquid and gas lumens 33and 34 have a larger size than in the distal shaft section 40. Forexample, in the main shaft section 39, the liquid and gas lumens eachmay have an I.D. of approximately 0.010 to 0.030 inches. At a mostproximal end where the main shaft section 39 connects to the manifold24, the lumens may be even larger. In the distal shaft section 40, theliquid and gas lumens taper to a much smaller I.D. with the liquid lumenapproximately 0.002 to 0.008 inches or even smaller and the gas lumen0.002 to 0.020 inches. In a preferred embodiment, the liquid and gasorifices 35 and 36 are less than 0.125 inches apart, and more preferablyless than 0.030 inches apart, and in a most preferred embodiment lessthan 0.001 inches apart. In a nebulizing catheter having an overalllength of 45 cm, the main shaft section 39 may be approximately 25 cmand the distal shaft section 40 may be approximately 20 cm. Also,although the liquid and gas lumens are shown to be side by side in FIG.2A, they may also be constructed to have an coaxial or otherarrangement. Further, although the main shaft section 39 is shown to beof a uniform diameter and profile, alternatively it may also have atapered diameter and profile such that the entire shaft 38 is taperedalong its length.

In a first preferred embodiment of the invention, as shown in FIGS. 1and 2, the nebulizing catheter 20 is removable, and replaceable withrespect to the endotracheal tube 10. This provides several significantadvantages. First, the nebulizing catheter 20 may be specificallyadapted and chosen to have the desired operating characteristicssuitable for delivery of the particular medication being administered tothe patient. In addition, the fact that the nebulizing tube 20 isremovable and replaceable provides versatility and flexibility regardingthe therapy and dosage regime that can be chosen by the physician. Forexample, a decision by the physician whether to deliver a medication tothe respiratory tract, and the selection of the type and dosage of themedication to be delivered, need not be made by the physician untilafter the endotracheal tube is already in place in the patient. When thephysician determines the proper type of medication to the delivered tothe patient via the respiratory tract, the appropriate nebulizationcatheter can be selected and inserted into the endotracheal tube.Further, the nebulizing catheter 20 can be removed after it is used andtherefore it is not necessary for the nebulization catheter to be leftin the patient and occupy space in the patient's respiratory tract or inthe endotracheal tube 10 when it is no longer needed. In addition, thedecision regarding the proper type of medication can be revisited againat any time after the endotracheal tube is in place. If a different typeof nebulizing catheter is required, such as for sterility purposes, theendotracheal tube need not be replaced as well.

Another advantage of providing the nebulization catheter as a separate,removable device is that it can be accommodated in a variety of otherinstruments and/or devices. For example, the nebulization catheter ofFIGS. 1-5 is shown used in an endotracheal tube; however, thenebulization catheter could also be positioned inside of a bronchoscope,such as in a working channel of a bronchoscope. The nebulizing cathetercould be positioned in any instrument that is positioned in therespiratory tract and that can accommodate the nebulizing catheter size.

The nebulizing catheter may be provided with radiopaque markings 41 tofacilitate positioning and placement. The radiopaque markings 41 may beprovided by radiopaque bands of metal or heat shrunk bands of dopedradiopaque plastic that are attached to the nebulizing catheter, oralternatively the markings may be provided by doping the plasticmaterial of the nebulizing catheter with a radiopaque material.Alternatively, a radiopaque dye may be added to the liquid beingdelivered by the nebulization catheter to assist observation. Themarkings 41 may be graduated to facilitate recognition, or alternativelymay extend over a portion or all of the nebulizing catheter. In still afurther embodiment, the markings may be formed of a ultrasonicreflectors, e.g. textured material, that are visible by means ofultrasonic imaging. The nebulization catheter may also include a stripe43 extending along a side of the shaft (as shown in FIGS. 5 and 6). Thestripe 43 may be radiopaque or ultrasonically visible and may be used todetermine the rotational orientation of the shaft. The stripe may beformed by a coextrusion process or by embedding a wire in the wall ofthe nebulization catheter.

One method that may be employed to facilitate positioning of thenebulization catheter is to monitor the pressure at the distal end ofthe endotracheal tube as the nebulization catheter is being advanced.Monitoring the pressure at the end of the endotracheal tube may beaccomplished through one of the endotracheal tube lumens. The gas sourceconnected to the proximal end of the nebulization catheter may beoperated so as to expel a gas from the distal end of the nebulizationcatheter as it is being advanced. The gas being expelled from the distalend of the nebulization catheter affects the pressure being detectedthrough the endotracheal tube. When the distal end of the nebulizationcatheter passes the distal end of the endotracheal tube, the pressurebeing measured through the endotracheal tube abruptly changes therebyproviding a clear indication of the location of the distal end of thenebulization catheter relative to the endotracheal tube.

The nebulizing catheter may also include a safety stop 44 located alonga proximal portion that engages a portion of the endotracheal tubeproximal portion or a fitting thereon, as shown in FIG. 2. The safetystop 44 ensures that the distal end of the nebulizing catheter 20 iscorrectly positioned with respect to the distal end 46 of theendotracheal tube 10 and prevents the distal end 37 of the nebulizingcatheter from extending too far into the trachea. In addition to thesafety stop 44, the proximal portion of the nebulizing catheter 20 mayalso have graduated markings 48 that would be visible to the physicianhandling the proximal end of the nebulizing catheter to enable adetermination of the position of the distal end 37 of the nebulizingcatheter 20 relative to a distal end 46 of the endotracheal tube 10.

The nebulizing catheter 20 may also include a critical orifice 49located at a proximal portion of the nebulizing catheter. The criticalorifice 49 may be formed by a small critical opening located in linewith the gas pressurization lumen 34 of the nebulizing catheter shaftclose to the manifold 24. The critical orifice 49 is sized so that ifthe nebulization catheter is supplied with a flow in excess of itsdesigned operating flow, the critical orifice will allow only thedesigned operating flow to pass through to the distal gas orifice.Alternatively, a safety valve may be located in the proximal portion ofthe catheter shaft. The safety valve would be designed to open ifsupplied with an excess of pressure.

In addition, the nebulizing catheter may include a centering device 50.The centering device 50 is located close to a distal end of thenebulizing catheter shaft and helps to center and align the distal endof the nebulizing catheter for improved performance, as explained inmore detail below.

According to one embodiment, the removable nebulization catheter 20 isenclosed in a storage sheath 51. The storage sheath 51 may be similar tothe type of storage sheaths used in conjunction with suction catheters.The storage sheath is preferably flexible, collapsible, or extendable toaccommodate insertion of the catheter. The storage sheath 51 may beconnected to the fitting 14. The storage sheath 51 can be used toreceive the nebulizing catheter 20 when it is being withdrawn from theendotracheal tube 10. The storage sheath 51 is sealed and can maintainthe withdrawn nebulizing catheter in an isolated condition when it istemporarily removed from the patient's respiratory system. The storagesheath 51 also allows the physician to re-insert the nebulizationcatheter into the patient. In this manner, the nebulization catheter canbe reused in a limited way with respect to a patient and can bemaintained in a sterile condition while withdrawn from the patient. Thestorage sheath 51 may have a distal sleeve 53 that can slide along theshaft of the nebulization catheter so that the nebulization catheter maybe advanced into the ventilation lumen of the endotracheal tube orwithdrawn into the storage sheath 51. The sleeve 53 may have a closefitting seal 55 located therein which is designed to clean and/or washthe nebulization catheter when it is withdrawn into the sheath.Alternatively, a cleaning seal 55 may be located in the port 16 ofmanifold fitting 14.

Another feature that may be used in conjunction with certain proceduresis radiation shielding. Some procedures for which the nebulizationcatheter may be used may involve the delivery of radioactive agents,e.g. tracers to the lungs. To minimize exposure to radioactivematerials, the nebulizing catheter may be provided with shielding overall or a significant portion of the overall length of the catheter.Shielding may also be provided at the liquid source reservoir.

The nebulizing catheter is preferably constructed of a biocompatible,chemically resistant polymer in order that it is suitable for use with awide variety of drugs. The catheter shaft is preferably clear to allowvisualization of contaminants or blockages of the interior lumens. Also,the portion of the catheter shaft that forms the liquid lumen 33 ispreferably composed of a relatively non-compliant material. In a presentembodiment, the catheter shaft is composed of a polymer such aspolyethylene or nylon. A polymer tubing is extruded with multiple lumensto be used for the separate gas and liquid lumens. In order to produce anebulization catheter with the tapered distal section 40, a multi-lumenextruded tubing may be drawn down in a portion thereof to form thetapered distal section 40. The draw down ratio may be selected toprovide a nebulization catheter shaft with the desired dimensions. Thedraw down process serves to make the lumens smaller in size distally aswell as closer together while maintaining the proximal cross sectionalprofile of the multi-lumen tubing. The larger proximal profile providesfor greater pushability in the catheter shaft and facilitatesmanufacturing by making the manifold connection easier. The draw downratio used on the extruded polymer tubing may be on the order of 2-to-1,5-to-1, or even as high as 20-to-1 or higher. Prior to drawing down, theextruded polymer tubing is preferably exposed to high energy radiationto crosslink the polymer molecules to provide for favorable materialproperties, such as the ability to maintain orifice dimensions andtolerances. The radiation may have an energy of approximately 10-700kgy. After the crosslinking step, the tubing is heated to its transitiontemperature between its melt and glass states, and is drawn down by thedesired ratio.

As an alternative to drawing down the extruded tubing, the multi-stagenebulization catheter shaft may be formed by a bubble extrusion processwherein the desired tapered distal section is formed directly in theshaft as it is being extruded. Again, this process may be used formanufacturing efficiency and convenience. As another alternative, themulti-stage shaft may be formed by a combination of both bubbleextrusion and drawing down. Still another alternative for forming thedesired tapered profile for the nebulizing catheter shaft is to use amaterial that can be cold drawn in order to cause a sharp neck down indiameter, such as a linear low density polyethylene. Although theprocess for forming the tubing is particularly suited for producing anebulization catheter shaft for use in delivering medicine to therespiratory tract, it should be understood that the process could beused to produce aerosol nozzles for non-medical purposes as well.

Alternatively, all or part of the nebulization catheter shaft can bemolded, especially at locations where close tolerances are preferredsuch as at the tip.

After the shaft is formed with the desired stages, it is cut andassembled with the other components of the nebulizing catheter. Althoughthe nebulization catheter is preferably constructed of a polymer, in analternative embodiment it could be formed of other materials such as ametal, especially a malleable metal to facilitate drawing, shaping orforming orifices. During the manufacturing process, the nebulizingcatheter may be pre-sterilized by means of a conventional process, suchas a gamma ray or electron beam. The nebulizing catheter is preferablydisposable after use with a single patient, but may be reused to alimited extent with a single patient provided that contamination can beprevented such as through the use of the sheath 51, described above. Thenebulizing catheter shaft preferably possesses torsional rigidity sothat rotation of the proximal end is transmitted at a 1:1 ratio to thedistal end. The nebulizing catheter may also be provided with anantiseptic coating.

Drug delivery rates are closely related to the particle size with largerparticles providing greater delivery rates. The embodiments of thenebulization catheter described herein have the capability of generatingparticle distributions with a GSD between 2 and 2.5. Drug delivery ratesin a range between approximately 5 and 1000 mg (0.005-1.0 ml) per minutemay be obtained. A variety of particle size distributions can begenerated at most flow rates through selection of the catheter type andaerosol volume output. An aerosol of this type can be generated with thenebulization catheter using a gas flow rate as low as 0.1 liter/minute.

There are a number of factors that affect the particle size generated.These factors include: (1) the gas orifice diameter, (2) the liquidorifice diameter, (3) the liquid delivery tube outer diameter andgeometry, (4) the distance between the gas and liquid orifices, (5) therate of gas delivery, and (6) the pressure of the liquid. Of course, thesize of the solid particles in suspension, if present, in the liquid area defining aspect of the aerosol particle size generated. In addition,there are other factors that affect the aerosol particle size such asthe characteristics of the liquid, e.g. viscosity, suspension, surfacetension and the composition of the driving gas, however, these factorsaffect the particle size of the aerosol generated to a lesser degree. Byselectively varying these parameters, the size and size distribution ofthe aerosol particles can be changed from less than a micron to at least10 microns.

The embodiments of the present invention, described herein are suitablefor delivery of an aerosol by nebulization with a volumetric particlesize distribution comparable to other nebulization systems. Further, bygenerating an aerosol at a location in the trachea or even deeper in thebronchi, impaction losses in tract can be avoided. By reducing impactionlosses, it may be acceptable to use larger particle sizes (e.g. greaterthan 5 microns). The combination of lower impaction losses and largerparticle sizes may provide higher effective delivery rates than priorsystems. Reducing impaction losses would enable an embodiment of thenebulization catheter to provide acceptable delivery rates with aerosolparticle sizes greater than 5 microns.

Referring to FIGS. 3-5, there is depicted a further embodiment of thepresent invention. According to the embodiment of FIGS. 3-5, there isprovided an endotracheal tube 52 and a nebulizing catheter. Thenebulizing catheter may be similar to the nebulizing catheter 20 shownin FIGS. 1 through 3. In the embodiment of FIGS. 3-5, the endotrachealtube 52 has an auxiliary lumen 56 in addition to its main ventilationlumen 60. Some endotracheal tubes provide auxiliary lumens through theshaft wall. The auxiliary lumen 56 is preferably sized and adapted toreceive the separate nebulization catheter 20. This embodiment providesmany of the same advantages as the embodiment of FIGS. 1 through 3. Inaddition, in this embodiment, the auxiliary lumen 56 may be providedwith a distal aperture 64 that facilitates locating and aligning thedistal end of 37 the nebulizing catheter 20 at a desired location fornebulization purposes.

In the embodiments of the invention shown in FIGS. 1-5, the nebulizingcatheter 20 is shown used in conjunction with an endotracheal tubeeither of a conventional type 10, as in FIGS. 1 and 2, or of a typeespecially designed for use with the nebulizing catheter such asendotracheal tube 52 of FIGS. 3-5. The nebulizing catheter 20 accordingto an embodiment of the present invention may also be used without aseparate endotracheal tube, i.e. the nebulizing catheter may be used ona patient who is not intubated, as shown in FIG. 6. If used on aspontaneously breathing patient (without an endotracheal tube), thepatient should be properly anesthetized and/or that the airway passageof the patient be topically anesthetized. The nebulizing catheter 20 ispositioned in the respiratory system of a patient directed past thecarina 68 into one of the bronchi 72 of the lungs. Alternatively, thenebulizing catheter 20 may also be positioned proximal of the carina inthe trachea, as desired. Embodiments of the nebulizing catheter may alsobe used on patients who have had tracheotomies or who have tracheotomytubes.

In the embodiment of FIG. 6, a guiding sheath 73 is used. The guidingsheath 73 is used to help position the nebulizing catheter 20 in therespiratory system of the patient. The guiding sheath 73 includes alumen through which the nebulization catheter 20 can be advanced into adesired bronchi site. To facilitate positioning the nebulizationcatheter, the guiding sheath 73 may have a pre-shaped distal end tofacilitate locating the sheath in the desired airway passage.Alternatively, the guiding sheath 73 may have a distal end that can beformed into a desired shape by the physician just prior to insertion.The guiding sheath 73 differs from the endotracheal tube 10 of FIGS. 1-5in that it may have a smaller outside diameter so that it can beadvanced into smaller airway passages deep in the patient's bronchi pastthe carina 68. The inside diameter of the sheath 73 is large enough toadvance the nebulization catheter. The guiding sheath 73 is particularlyuseful when the nebulization catheter 20 is being located deep in thepatient's lungs, or when the nebulization catheter is used without anendotracheal tube. The guiding sheath 73 may also be used with anendotracheal tube through the ventilation lumen thereof. The guidingsheath is preferably composed of a torsionally rigid material so thatthe distal end of the guiding sheath is responsive to rotation at theproximal end.

Referring to FIGS. 7 and 8, there is shown another embodiment of thenebulizing catheter. In the embodiment of FIG. 7, a nebulizing catheter76 includes an occlusion balloon 80 located on a distal exterior surfaceof the nebulizing catheter shaft body 84. The nebulizing catheter 76 mayinclude an additional lumen 88, as shown in FIG. 8, located therethroughand communicating with the interior of the balloon 80 for providinginflation fluid, i.e. preferably gas, to expand the occlusion balloon80. This lumen 88 for inflation fluid is in addition to the lumens 92and 96 in the catheter shaft 84 used for conveyance of the liquidmedicine and pressurized gas, respectively. The occlusion balloon 80 maybe used to position the nebulizing catheter in the appropriaterespiratory branch 100, center the nebulizing catheter tip for properorientation, and isolate a particular bronchus, as needed. Theembodiment of the nebulizing catheter 76 shown in FIG. 7 may be usedwith an endotracheal tube in a manner similar to that shown in FIGS.1-3, or alternatively it may be used without a separated endotrachealtube, similar to the embodiment of FIG. 6. When used without a separateendotracheal tube, the nebulizing catheter 76 of FIG. 7 could be usedfor the purpose of selective ventilation of one of the bronchi of thelungs even without providing aerosolization. Alternatively, thenebulization catheter 76 could provide aerosolization on an intermittentbasis with continuous ventilation. If the nebulization catheter is usedto provide ventilation as well as aerosolized medication, theventilation regime can be tailored to maximize aerosol transport.

In addition, to further facilitate positioning and placement, thenebulizing catheter 76 may be used with a guide wire 104. The nebulizingcatheter may be provided with a separate guide wire lumen 108 to receivethe guide wire 104, or alternatively, the guide wire may use one of theexisting lumens that is also used for either the pressurized gas or theliquid or alternatively the guide wire may be incorporated and fixedinto the nebulizing catheter so that it is non-removable. The guidewire, whether of the removable type of the type that is fixed to thenebulizing catheter, may also be steerable, i.e. so that it can beguided from a proximal end to access the appropriate location in thelungs. The steering apparatus may utilize selective tensioning of a pullwire, etc. from a proximal end. If the guide wire is of the separateremovable type, it may be withdrawn after it has been used to positionthe distal tip of the nebulizing catheter so as to avoid interferingwith aerosol delivery. In addition, the distal tip of the guide wire ornebulization catheter may be pre-shaped or shapable by the physician soas to impart an appropriate curve or bend to facilitate access to thedesired airway.

Referring to FIG. 9, there is shown another embodiment of a nebulizingcatheter of FIG. 7. The embodiment of FIG. 9 is similar to theembodiment of FIG. 7 with the exception that the separate guide wire 104is received in a loop 106 located close to a distal end of thenebulizing catheter 76. Proximal of the loop 106, the guide wire 104 ispositioned adjacent to the shaft 84 of the nebulizing catheter 76.Instead of a loop 106, the guide wire may be received in a short lumenlocated in the distal end of the nebulizing catheter.

II. Generation of Aerosol Plume

It has been discovered that the shape of the aerosol plume can be asignificant factor affecting the rate and efficacy of the delivery ofmedication by an aerosol. In general, it is preferable to generate anaerosol that has a shape that minimizes particle impaction near thedistal tip of the nebulizing catheter, given the location of the tip andthe airflow conditions around it. For example, if the aerosol plume iswide, a portion of the drug may be wasted in the end of the endotrachealtube or on the wall of the trachea or other airway passage. On the otherhand, if the plume is too narrow or the velocity too high, a portion ofthe drug may impact excessively on the patient's carina. In general, alow aerosol particle velocity is desirable. One of the reasons for thisis to avoid impacting the carina with the discharge of high velocityaerosol particles. In addition, it is also generally desirable to haveas wide an aerosol plume as possible while avoiding significant impactwith the walls of either the endotracheal tube or the respiratory airwaypassage. The effects of aerosol plume velocity and geometry are relatedto anatomical factors. In some circumstances, e.g. away from the carina,a narrow, fast aerosol plume may be preferable to a slower, wider plume.

Regarding the embodiments described below, certain of the embodimentsmay be preferable from the standpoint of versatility, i.e. they may beable to deliver a variety of medications having different viscosities,suspensions, surface tensions, etc. Others of the embodiments may bemore suitable for the delivery of specific types of medications or thedelivery of particles of certain sizes.

Referring to FIG. 10, there is shown a tip configuration for anebulizing catheter 112. The nebulizing catheter 112 may be either astand alone-type of nebulizing catheter, similar to the catheters shownin FIGS. 6 and 10, or may be incorporated into an endotracheal tubeeither removably, as in FIGS. 1-5, or non-removably. In the embodimentof FIG. 10, the nebulizing catheter 112 has a coaxial configuration.Specifically, the nebulizing catheter 112 includes an outer tubularmember 116 defining a lumen 120 and an inner tubular member 124 alsodefining a lumen 128. The inner tubular member 124 is located in thelumen 120 of the outer tubular member 116. According to the embodimentshown FIG. 6, pressurized gas is conveyed in the annular region definedbetween the inner and outer tubular members. Liquid medication isconveyed in the lumen 128 of the inner member 124. As shown in theembodiment of FIG. 10, a distal end of the outer tubular member 116 isapproximately adjacent to a distal end of the inner tubular member 124.In the embodiment of FIG. 10, the outer tubular member 116 has an O.D.of approximately 0.008 inches and an I.D. of approximately 0.006 inches.The inner tubular member 124 has an O.D. of approximately 0.003 inchesand I.D. of approximately 0.0015 inches. Both the inner tubular member124 and the outer tubular member 116 have larger dimensions proximal ofthe distal tip portion. Along a main shaft portion proximal of thedistal tip, the outer tubular member 116 has an O.D. of approximately0.115 inches and an I.D. of 0.080 inches and the inner tubular member124 has an O.D. of approximately 0.060 inches and an I.D. of 0.050inches.

The embodiment of FIG. 11 shows a tip of a nebulizing catheter 132. Thisembodiment is similar to the embodiment of FIG. 10. The tip 133 isformed with a plurality of lumens terminating in a plurality oforifices. An inner lumen 134 is used to convey the liquid medication andthe surrounding lumens 135 convey the pressurized gas used to nebulizethe liquid. This embodiment has the advantage that the orifice of theliquid lumen 134 is centered with a fixed spacing relative to theorifices of the gas lumens 135 around it. In the embodiment of FIG. 11,the multiple lumen construction may extend all the way back to theproximal end of the nebulizing catheter 132 or alternatively, only adistal segment may have the multiple gas lumen configuration in whichcase the pressurized gas may be conveyed through a single proximal lumenthat connects to the multiple distal lumens.

FIGS. 12 and 13 show an alternative embodiment 136 of the multiple lumennebulization catheter in FIG. 11. The embodiment in FIGS. 12 and 13 isuseful when it is desired to provide the aerosol medicine with a pulseddelivery. The pulsed delivery may be timed to coincide with theinhalation of the patient so that aerosol is not wasted when the patientis exhaling. A potential drawback with pulsed delivery is that theaerosol may drool from the tip of the nebulizing catheter when thepressure being applied to the liquid is reduced to effect the pulsation.To avoid this potential problem, the nebulizing catheter 136 providesfor closure of the liquid lumen when the pressure being applied to it isreduced. As in the previously described embodiment, the nebulizationcatheter 136 in FIGS. 13 and 14, has a centrally located lumen 137 fordelivery of a liquid medicine and a plurality of lumens 138 surroundingthe central lumen 137 for conveyance of a pressurized gas to nebulizethe liquid at the distal orifice 139. In this embodiment, the catheter137 is formed of a low compliance material in the outer wall area 140and a relatively high compliance material in the area 141 surroundingthe centrally located liquid lumen 137. These differing compliancecharacteristics may be formed in the catheter shaft by coextruding asingle tube with different materials. When using the embodiment of FIGS.12 and 13, a constant, relatively high pressure is applied to the gas inthe lumens 138. Liquid medicine is delivered via the lumen 137 andpressure pulses are applied to the liquid from an external deliverysource, such as a pump. When the pressure in the liquid lumen 137 islow, the high pressure in the gas lumens 138 deform the compliant innermaterial 141 thereby compressing the liquid lumen 137 and closing itoff, as shown in FIG. 12. When a pressure pulse is applied to the liquidin the lumen 137, it overcomes the compressive forces from the gaslumens 138 allowing the lumen 137 to open and permitting the liquidmedicine to be delivered to the distal orifice 139 to be nebulized, asshown in FIG. 13. In this manner, the embodiment of FIGS. 12 and 13provides for pulsed liquid nebulization with reduced possibility ofdrooling.

Another feature shown in FIGS. 11 and 12 is a porous plug 142 located inthe liquid orifice 139. This porous plug may be made of a felt-likematerial and may assist in the production of fine aerosol particles.

The embodiment of FIG. 14 shows a distal tip of another embodiment ofthe nebulizing catheter. In this embodiment, a nebulizing catheter 148includes a main shaft section 152 and a distal shaft section 156. Thedistal shaft section 156 is tapered to a tip 160. At the tip 160, aliquid orifice 164 is surrounded by a plurality of gas orifices 168. Ina preferred embodiment, there are six gas lumens terminating in the sixorifices 168. In this embodiment, the liquid orifice 164 has a diameterof approximately 0.002 inches and the gas orifices 168 each have adiameter of approximately 0.002 inches. This embodiment is similar tothe embodiment of FIG. 11 except that the distal section 156 providesfor a reduction in the tip size and corresponding modification of thenebulization plume properties. This reduction is preferable as itprovides a smaller orifice size.

The embodiment of FIG. 15 shows a distal portion of a nebulizingcatheter 172. In this embodiment, the nebulizing catheter includes aproximal shaft section 176 and a distal shaft section 180. The proximalshaft section 176 includes a plurality of lumens 184. A central one 188of the plurality of lumens 184 is used to convey liquid medicine and theremainder of the lumens surrounding it are used to convey gas. Thedistal shaft section 180 connects to the distal end of the proximalshaft section 176 and defines a tapered cavity 192 between the distalend of the proximal shaft section 176 and a distal orifice 196. At leastone of the plurality of lumens 184 is used to convey a pressurized gasthat is discharged into the cavity 192. A tubular extension 200 extendsthe liquid lumen through the cavity 192 and distally out the orifice196. The orifice 196 is sized to provide an annular region around thetubular extension 200 to permit the pressurized gas to flow through tonebulize the liquid medication that exits a distal orifice 204 of thetubular extension 200. In a preferred embodiment, the distal shaftsection 180 is composed of stainless steel and the orifice has an I.D.of 0.025 inches. The tubular extension 200 has an O.D. of 0.012 inchesand an I.D. of 0.007 inches. This embodiment has the advantage ofcombining a relatively small distal profile with a relatively largeproximal flow channel. Another advantage of this embodiment it that itprovides for a balanced airflow around the liquid orifice 204.

FIG. 16 shows yet another embodiment for a tip for a nebulizingcatheter. In FIG. 16, a nebulizing catheter 208 has a coaxialconfiguration similar to the embodiment of FIG. 10 (although it couldalso have a configuration similar to that of other coaxial embodiments,e.g. FIGS. 11, 14, or 15). In FIG. 16, a thin solid wire or filament 212is located at a distal end of a liquid orifice 216 located at a distalend of an inner tubular member 220. The tapered wire 212 extends a shortdistance distally from the distal end of the inner tubular member 220.The tapered wire 212 is located with respect to the liquid orifice 212so that liquid being conveyed through the inner member 220 continues toflow distally of the distal orifice 216 along the wire 212, i.e.adhering to it by surface tension. Of course, once the liquid reaches adistal tip 224 of the wire 212, it is entrained and nebulized by the gasflow from the annular region 228 defined between the inner tubularmember 220 and an outer tubular member 232. As mentioned above, one ofthe factors that affects the nebulization plume particle size andgeometry is the size of the distal liquid orifice. In general, a smallerliquid orifice produces smaller particles and a narrow aerosol plumecone. In the embodiment of FIG. 16, the thin wire 212 carries only asmall amount of liquid along it so that it functions similarly to anorifice of a very small size. Accordingly, the embodiment of FIG. 16 hasthe potential for producing an aerosol of very fine particles. In theembodiment of FIG. 16, the outer tubular member has an I.D. ofapproximately 0.020 inches. The inner tubular member has an I.D. ofapproximately 0.006 inches. The thin wire has an O.D. of approximately0.002 inches. The wire or filament 212 may be composed of a metal wireor a polymer wire, such as a polyolefin fiber like Spectra fiber.Alternatively, the filament 212 may be composed of a porous or felt-likematerial, such as nylon or Porex, in which case it may be wider indiameter than if made of a solid material.

FIG. 17 shows an alternative embodiment of the embodiment of FIG. 16. InFIG. 17, there is a distal end of a nebulizing catheter 236 having atapered wire or filament 240 located at the distal end of a lumen of aninner tubular member 244. The tapered wire 240 in this embodiment has acurved shape that is designed to whip in a spiral when it is in a flowof air. In the embodiment of FIG. 17, when pressurized gas flows throughthe annular region 248, it causes the tapered wire 240 to whip aroundwith a spiral motion. The length of the wire 240 is chosen so that itdoes not impact the wall of the trachea or other airway passage when itmoves in a spiral whipping motion. In one embodiment, the wire 240 has alength of approximately 1-2 mm. The tapered wire 240 carries the liquidout to its tip for entrainment, and the nebulization plume is formedwith a conical shape. The width of the plume may be changed by changingthe length of the filament 240. The speed of the spiral motion can becontrolled by appropriate selection of wire stiffness and air foilshape. In general, the spiral plume produced by the embodiment of FIG.17 will be wider than the embodiment of FIG. 16 and have less forwardvelocity. Both these characteristics may be favored in a nebulizationcatheter.

FIGS. 18 and 19 show another embodiment of the nebulization catheter. Inthis embodiment, a nebulization catheter 252 has a coaxial configurationformed of an outer tubular member 256 and an inner tubular member 260. Adistal plug 264 fits into a distal end of the annular region 268 formingthe gas lumen. A plurality of apertures 272 extend through the plug 264to form distal gas orifices. Located in a lumen 276 defined by the innertubular member 260 is a retractable wire or pin 280. The wire 280 ispreferably a solid wire of a rigid material. For example, the wire maybe composed of a metal, such as stainless steel, a polymer, or aradiopaque material. A distal end 284 of the inner member 260 is taperedand may extend distally of the plug 264 or alternatively may extend onlyto the distal end of the inner tubular member 260 or even proximallythereof. The distal end of the inner member 260 terminates in a distalliquid orifice 285. A distal end 286 of the wire 280 may also betapered. The wire 280 is sized with respect to the inner tubular member260 so that the tapered distal portion 286 of the wire 280 seats againstthe tapered distal portion 284 of the inner tubular member 260 andthereby seals a distal end of the liquid lumen 276 in a manner similarto a needle valve. The wire 280 is retractable and in a preferredembodiment is operated to reciprocate back and forth to pulse thedelivery of liquid out the distal end of the nebulizing catheter 252.The pulsing of aerosol delivery may be adjusted to any suitable timeperiod. In one preferred mode of operation, the aerosol may be deliveredonly during inhalation by the patient. If the nebulizing catheter 252 isbeing used with an endotracheal tube and a ventilator, the pulsing ofthe aerosol delivery may be timed to coincide with the patient'sinhalation by an appropriate connection with the ventilator. By limitingthe delivery of medicine to only the period of time when the patient isinhaling, the medicine can be delivered more efficiently and with lesswaste.

One preferred way to generate the pulsed aerosol plume with theembodiment of FIGS. 18 and 19 is with a manifold arrangement 287. Aproximal end of the wire 280 is fixed to an extendable section 288 ofthe manifold 287. The wire 280 may be fixed by means of an elastomericseal 289. Pressurized gas is delivered to a port 290 of the manifoldthat communicates with the outer tubular member 256 and liquid medicineto be nebulized is delivered to a second port 291 that communicates withthe inner tubular member 260. The liquid medicine also fills the volume292 proximal of the port 291 in the expandable section 288. The wire 280is connected to the manifold so that the distal end of the wire isbiased against the distal end of the inner tubular member by theresilience of the inner tubular member 260 and/or the expandable section288. Pulsed pressurization of the liquid medicine from the source causesthe extendable section 288 to reciprocate back and forth as shown by thearrow 293. Since the proximal end of the wire 280 is attached to theexpandable section 288 proximal of the port 291, application of pressurepulses to the liquid causes the proximal end of the wire 280 toreciprocate back and forth as well. This causes the distal end of thewire 280 to reciprocate back and forth in the seat 284. Application ofpressure pulses to the liquid medicine can be timed to coincide with thepatient's inhalation. Alternatively, instead of forming an expandable orcompressible section at the manifold, the shaft of the inner tubularmember 260 may be formed of a stretchable material so thatpressurization of the liquid causes retraction of the wire as the entireshaft elongates. Other alternatives for effecting reciprocatingoperation of the wire 280 are use of an electro- mechanical, mechanical,hydraulic, or pneumatic actuator to drive the wire. Aside from providingfor pulsed delivery of the aerosol, this embodiment of the nebulizationcatheter has the further advantage that the reciprocating action of thewire may assist in keeping the orifice free of any blockages which mayoccur, especially with some viscous solutions or suspensions.

In a manner similar to the embodiments 208 and 236 of FIGS. 16 and 17,in the embodiment 252 of FIGS. 18 and 19, the distal tip of theretractable wire 292 can extend distally from the distal liquid orifice288 in order to minimize particle size, or alternatively may not extenddistally of the distal liquid orifice 292. In one embodiment, the distaltip of the retractable wire may extend distally of the liquid orifice288 by approximately 0.2 mm.

FIG. 20 shows another embodiment of a nebulizing catheter. In thisembodiment, a nebulizing catheter 296 has a main shaft portion 300 witha gas lumen 304 adjacent to a liquid lumen 308. The gas and liquidlumens 304 and 308 flow into a distal cavity 312. The distal cavity 312is formed by an outer tubular extension 316 that extends distally overand past a distal end 320 of the main shaft portion 300. A filter 324 islocated in the liquid lumen 308 to filter out any particles in theliquid. The liquid lumen 308 has a step down in diameter immediatelydistal of the location of the filter 324. An insert plug 328 is locatedin a distal end of the outer tubular extension 316. The insert plug 328(which may be a sapphire jewel, for example) has an aperture 332 throughit that forms an exit orifice from the cavity 312. The insert plug 328has a conical shaped proximal profile facing the cavity 312. An innertubular extension 336 fits into the stepped down portion of the liquidlumen 308 and extends the liquid lumen 308 into the cavity 312. A distalend 340 of the inner tubular extension 336 terminates in the cavity 312.Since the gas lumen 304 exits into the cavity 312, nebulization of theliquid takes place at the tip of the inner tubular extension 336 insidethe cavity 312. This region of the cavity 312 is a positive pressureregion due to the relative sizes and locations of the apertures. Thepositive pressure in this region may have the effect of reducingdrooling of the liquid medicine as it leaves the orifice of the tubularextension 336. The aerosol exits the catheter 296 via the aperture 332and the aerosol plume is defined in part by the positive pressure in thecavity 312 and the aperture size. In this embodiment, the main shaftportion and the tubular extension are composed of a suitable plasticsuch as polyethylene. The filter is composed of multiple 50 μm I.D.tubes or similar course filter material. The gas and liquid lumens mayeach have an I.D. of 0.010 to 0.015 inches The inner tubular extension336 may be formed of polyimide tubing with an I.D. of 0.004 inches andan O.D. of 0.010 inches. The outer tubular extension 316 may be formedof a heat shrunk tubing, such as polyethylene. The plug 328 may have anO.D. 0.087 inches and the aperture 332 in the plug 328 may have adiameter of 0.007 inches.

FIG. 21 shows another embodiment of the nebulizing catheter. Thisembodiment is similar to the embodiment 296 shown in FIG. 20 andaccordingly the components are numbered similarly. The embodiment ofFIG. 21 differs from the embodiment of FIG. 20 in that the distal end ofthe inner tubular extension 312 is located in the aperture 332 of theinsert plug 328. In the embodiment of FIG. 21, the orifice 332 at thedistal end of the tubular extension 336 is in a low pressure, highvelocity region as compared to the embodiment of FIG. 20. This has acorresponding effect on plume size and shape as well as possibleparticle size.

FIG. 22 shows yet another embodiment for the nebulizing catheter. Inthis embodiment, a nebulizing catheter 340 has a main shaft portion 344that has a gas lumen 348 and a liquid lumen 352. The gas lumen 348terminates distally in a gas orifice 356. Located in the distal end ofthe liquid lumen 352 is a liquid tubular extension 360. The liquidtubular extension 360 forms an angle so that a distal liquid orifice 364is in alignment with the flow of gas out the distal gas orifice 356. Inthis embodiment, the liquid lumen 352 has an I.D. in the range of 0.010to 0.020 inches. The gas lumen 348 has an I.D. of approximately 0.10 to0.020 inches. The liquid tubular extension 360 is formed of a stainlesssteel tube with an O.D. of 0.018 inches and an I.D. of 0.012 inches. Thedistal gas orifice 356 has an I.D. of 0.010 inches. The stainless steelextension tube 360 forms a right angle so that the distal liquid orifice364 is at a right angle and aligned with the distal gas orifice 356. Thedistal gas orifice 356 and the distal liquid orifice 364 are positionedas close together as possible, and in one embodiment, these orifices areapproximately .010 inches apart.

FIG. 23 shows an alternative embodiment of the nebulization cathetershown in FIG. 22. In this embodiment, the nebulization catheter 340 hasan additional lumen 365. This additional lumen 365 may have an I.D. ofapproximately 0.020 inches. This additional lumen 365 may be used for anoptical fiber viewing scope 366 for illumination and visualization ofthe distal end of the nebulization catheter 340. The optical viewingscope 366 may be permanently installed in the catheter 340 or preferablymay be removable. A distal end 367 of the lumen 365 is open or coveredwith a transparent lens so that the area distal of the catheter 340 canbe observed via an optical viewing device connected to a proximal end ofthe optical fiber 366. This enables a physician to observe the alignmentof the distal end of the nebulization catheter and also observe thenebulization when it occurs. The gas orifice 356 may be located so thatthe pressurized gas that is expelled helps to keep the distal end of theviewing lumen 365 clear. An optical fiber viewing channel may beincorporated into any of the embodiments of the nebulization catheterdisclosed herein. When the additional lumen 365 is occupied by aremovable viewing scope, it may be used for other purposes such aspressure sensing, gas sampling, over pressure relief, or otherdiagnostic or therapeutic purposes. Alternatively, another lumen may beprovided for these purposes.

The embodiment of FIG. 23 also shows opposing orifices. As in theembodiment of FIG. 22, a tubular extension 360 extends distally of theend of the catheter shaft and is oriented at an angle, e.g. 90 degrees,to the direction of the axis if the catheter shaft. The tubularextension 360 opens to a distal liquid orifice 364 from which the liquidbeing conveyed in the lumen 352 exits. In this embodiment, a secondtubular extension 363 communicates with the gas lumen 348 and opens to adistal gas orifice 367. The second tubular extension 363 is alsooriented relative to the axis of the catheter shaft, e.g. by 90 degrees,so that is aimed toward the distal liquid orifice 364 in order tonebulize the liquid exiting from the liquid orifice 367.

FIG. 24 shows still another embodiment of the nebulizing catheter. Inthis embodiment, a nebulizing catheter 368 has a main shaft section 372with a gas lumen 376 and a liquid lumen 380. Tubular extensions 384 and388 extend the gas and liquid lumens 376 and 380 from the main shaftsection 372 to a distal tip of the catheter 368. The distal portion ofthe shaft forms a tapered region 392 that surrounds the tubularextensions 384 and 388 and causes them to be angled toward each other.The tubular extension 388 for the liquid lumen 380 extends slightlydistally of the distal end of the tubular extension 384 of the gas lumen376 so that a distal liquid orifice 396 is in alignment with the flow ofgas from a distal gas orifice 400. In this embodiment, the distal liquidorifice 396 has an O.D. of 150 microns and an I.D. of 20 microns. Thegas orifice 400 has an I.D. of approximately 0.018 inches.

FIGS. 25 and 26 show an alternative embodiment of the nebulizingcatheter 368 shown in FIG. 24. In FIGS. 25 and 26, the tubularextensions 384 and 388 of the gas lumen 376 and the liquid lumen 380 areformed with sealable tips. Specifically, the gas tubular extension 384has a sealable tip 408 and the liquid tubular extension 388 has asealable tip 412. Alternatively, only the liquid lumen 380 has thesealed tip 412 and the gas lumen 376 has an open distal orifice. Thesealable tips may be formed by heating the material from which thetubular extensions are made to reform the walls of the plastic materialso as to form a closed slit. This is represented in FIG. 26. Whenpressurized gas and liquid are conveyed through the lumens 376 and 380,the slits forming the tips 408 and 412 dilate thereby permitting the gasand liquid to exit to from the aerosol, as illustrated in FIG. 25.However, when the pressure in the lumens 376 and 380 falls below athreshold, the tips 408 and 412 close thereby sealing off the lumens, asillustrated in FIG. 26. The embodiment 404 of the nebulizing catheter isused with pulsation of the gas and/or liquid supplies. In order to pulsethe generation of aerosol to coincide with a patient's inhalation, thepressure to the gas and/or the liquid lumens can also be pulsed. Whenthe pressure in either of the lumens falls below a threshold, the tips408 or 412 close. By closing off the flow of liquid at the tip 412during the period when the aerosol is not being generated, it ispossible to reduce any drooling from the tip of the catheter.

III. Nebulization With Counterflow

As mentioned above, control of nebulized particle size and plume shapeare important considerations affecting the efficacy of the therapy. Inmany applications, it is preferable to have as small a particle size aspossible combined with as little forward velocity as possible. Some ofthe embodiments described below accomplish these objectives through useof counterflow arrangements.

FIG. 27 shows a nebulization catheter 416 that can be located inside ofan endotracheal tube as in the previously described embodiments. Thenebulization catheter 416 has a coaxial tubular arrangement with anouter tube 417 surrounding an inner tube 418 so that a liquid deliveredfrom a distal liquid orifice 419 of the inner tube 418 is nebulized bythe flow of a pressurized gas delivered in a distal direction from theannular region between the inner and outer tubes at the distal orifice420 of the outer tube 417. In addition, another lumen 428 extendsthrough the shaft of the nebulization catheter 416. This additionallumen 428 connects to a distal tubular extension 432. The tubularextension 432 extends distally of the distal end of the nebulizationcatheter 416. A distal end 436 of the distal tubular extension 432curves back on itself so that a distal orifice 440 of the tubularextension 432 is oriented in a proximal direction back at the orifices419 and 420 of the inner and outer tubes. The additional lumen 428 alsocarries a pressurized gas which is directed in a proximal direction bythe orifice 440 against the direction of the aerosol plume generated bythe gas and liquid exiting the orifices 419 and 420. The gas from theadditional lumen 428 presents a counterflow to the gas from theseorifices thereby slowing down the velocity of the particles generatedfrom these orifices. In a preferred embodiment, the distal tubularextension 432 may be formed of a suitable material such as stainlesssteel needle stock. The O.D. of the nebulization catheter in thisembodiment may be similar to the other nebulization catheter embodimentsdescribed above, e.g. O.D of approximately 0.038 inches. The distaltubular extension 432 may have an O.D. of approximately 0.013 inches andan I.D. of approximately 0.009 inches. In this embodiment, the outertubular member of the nebulization catheter may have an O.D. ofapproximately 0.013 inches and an I.D. of approximately 0.009 inches andthe inner tubular member may have an O.D. of approximately 0.003 inchesand an I.D. of approximately 0.0015 inches.

FIG. 28 shows another embodiment of the present invention for anebulizing catheter 448 that incorporates a counterflow arrangement.Like the embodiments described above, in this embodiment the nebulizingcatheter 448 may be located in an endotracheal tube (not shown). Thenebulization catheter 448 has a distal section 452 that curves back onitself. The nebulization catheter 448 has distal orifices 453 and 454that generate a plume of nebulized particles in a reverse, i.e.proximal, direction. Also located in the nebulization catheter 448 isanother lumen 456 for carrying a pressurized gas. The additional lumen456 has a distal orifice 460 oriented in a distal direction. The distalorifice 460 of the additional lumen 456 is aligned with respect to thedistal orifices 452 and 453 of the nebulization catheter 448 so that theflow of gas from the additional lumen 456 slows down the velocity of thenebulization plume generated from the nebulization catheter 448. Theaerosol plume generated by the nebulization catheter reverses directionand is delivered to the lungs carried by the inhalation of air throughthe endotracheal tube or by the flow of gas from the additional lumen456 or a combination thereof.

FIGS. 29 and 30 show another embodiment of a counterflow nebulizationcatheter arrangement. In FIGS. 29 and 30, a nebulizing catheter 464 isused with an endotracheal tube 468. A nebulization catheter 464 has adistal tip 472 from which a liquid medicine delivered from a distalliquid orifice is nebulized by a flow of pressurized gas from a gasorifice located adjacent to the liquid orifice. The nebulizing catheter464 shown in FIG. 30 extends distally of the endotracheal tube 468 andhas a distal section 476 that curves back on itself. The nebulizationcatheter 464 has distal orifices that generate a plume of nebulizedparticles in a reverse, i.e. proximal, direction back toward the distalopening of the endotracheal tube 464. In order to maintain a properreverse orientation and to prevent snagging, the nebulization catheter464 includes a wire 480 that extends from the tip 472 of thenebulization catheter 464. The wire 480 is secured to a portion of theshaft of the nebulization catheter proximal of the tip. The wire 480 canbe secured by means of a heat shrunk tube 484 located on a shaft 488 ofthe catheter to hold the end of the wire 480. Although some aerosol mayimpact the wire 480, a wire having a small diameter is used to minimizelosses due to such impaction. Moreover, the overall improved efficiencydue to reduction in aerosol impaction on the walls of the trachea orother airway passage is expected to more than compensate for any lossesdue to impaction on the wire 488.

In the embodiment shown in FIG. 30, the nebulization catheter 464directs a nebulization plume in a reverse direction back toward thedistal opening of the endotracheal tube 468. The nebulization plume fromthe nebulization catheter encounters the flow of air from theendotracheal tube 468 during the inhalation phase of the patient. Theinhalation of air through the endotracheal tube 468 causes the nebulizedmedicine to reverse direction and carries it to the lungs. It is notedthat the reversal of direction of the nebulization plume has the effectof minimizing the aerosol particle velocity. It is also noted in theembodiment shown in FIG. 30 that the endotracheal tube 468 is providedwith an inflatable cuff 492 located around the distal portion.

IV. Other Nebulization Catheter Embodiments

In the embodiments described above, the velocity of the nebulizationplume was reduced by use of a counterflow of gas in an oppositedirection. In the embodiment of FIGS. 31 and 32, the velocity of thenebulization particles is reduced in another manner. In FIG. 31 anebulization catheter 496 has a liquid lumen 500 terminating in a distalliquid orifice 504 and a one or more gas lumens 508 terminating in oneor more distal gas orifices 512. The liquid delivered through the liquidlumen 500 is nebulized by the pressurized gas flowing out the pluralityof gas orifices 512. The nebulization catheter 496 also includes one ormore additional lumens 516 that terminate in additional distal orifices520. These lumens 516 are used to deliver a vacuum (negative pressure)at the distal orifices 520. The vacuum is provided by a suitable vacuumsource (not shown) connected to proximal ends of the additional lumens516. The vacuum delivered by the additional lumens 516 helps withdrawthe pressurized gas delivered by the lumen 508 after it has nebulizedthe liquid delivered by the liquid lumen 500. Without the vacuumprovided by the additional lumens 516, the pressurized gas delivered bythe distal gas orifices 512 may continue to impart energy to thenebulized liquid particles delivered by the distal liquid orifice 504thereby causing them to be propelled with a forward velocity. Instead,the vacuum scavenges at least some of the pressurized gas after it hasnebulized the liquid so that the forward velocity of the liquidparticles can be reduced. In order to facilitate scavenging of thepressurized gas, the distal liquid orifice 504, the distal gas orifices512, and the distal vacuum orifices 520 all open into a distal cavity524 formed by an outer tubular extension 528 of the nebulizing catheter496. The distal extension 528 has a closed distal end 532 with a smallaperture 536 located therein to emit the nebulized liquid particles witha low forward velocity. With the nebulizing gas removed, the aerosolparticles are carried forward primarily only by their inertia.

The embodiment of the nebulization catheter 496 shown in FIG. 31includes a vacuum line 516 as a means to reduce the forward velocity ofthe nebulization plume. Provision of vacuum line 516 to the tip of anebulization catheter 496 can serve an additional function of balancingthe gas flow and pressure delivered to the airway in which thenebulization catheter is located. This may be useful to prevent excessairway pressure generated by the catheter flow particularly in smallerairways or where a neutral flow balance may be desired. This mayparticularly be desired when the nebulization catheter is provided withan inflatable cuff that occludes the airway passage at the distal end ofthe nebulization catheter. The flow balance may be controlled with aclosed or partially closed pumping system where a gas pump 537 with asingle intake and outlet would be connected to the respective vacuum andgas supply lumens 516 and 508 of the catheter. Both the driving gas andvacuum would be balanced and regulated by the pump speed. A vacuum orpressure vent port 538 could be incorporated into the respective vacuumor pressure lines if a positive or negative flow balance was desired. Ifflow balance is a concern, but not velocity reduction, it is notimportant where the air flow is removed at the distal tip of thecatheter and accordingly, the distal end extension 532 may not beneeded. Alternatively, a flow balance may be maintained with separate apressure and vacuum source through the use of regulators, restrictivecapillary tubes or orifices, or flow sensors and flow control valvesincorporated into the pressure and vacuum supply lines.

FIG. 33 shows another embodiment of a nebulization catheter 540 thatincorporates a feature to reduce the forward velocity of the nebulizedliquid particles. The nebulization catheter 540 has a main shaft portion544 having a liquid lumen 548 and a pressurized gas lumen 552. Thelumens 548 and 552 terminate in distal orifices 556 and 560. Thepressurized gas flow from the orifice 560 nebulizes the liquid exitingfrom the orifice 556. The nebulization catheter 540 includes a distalspacer tube 564. The spacer tube 564 has a length of approximately 2-3mm and an inside diameter larger than the outside diameter of thenebulization catheter shaft 544. Because the inside diameter of thespacer tube 564 is larger than the airflow lumen and orifice, thevelocity of air and entrained particles is reduced as they pass throughthe spacer tube 564 and out a distal opening 568 thereof. In addition,the spacer tube 564 may have one or more apertures or holes 572 througha wall thereof close to the proximal end of the spacer tube at itsconnection to the main shaft 544. These holes 572 draw in air to theinside of the spacer tube 564 thereby causing drag due to turbulence andreducing the velocity of the aerosol as it exits the spacer tube. Theholes 572 may also slow the flow of particles through the spacer tube bycausing drag turbulence.

The spacer tube 564 also serves to protect the distal orifices 556 and560 of the nebulization catheter from coming into contact with any partof the endotracheal tube, trachea, or other airway passage therebyhelping to maintain optimum tip operation and to prevent damage to itduring handling and insertion. In an alternative embodiment, if only thetip protection feature is desired, the spacer tube 564 of FIG. 33 may beprovided without the apertures 572. In such an alternative embodiment,the spacer tube 564 may be provided in a shorter length, e.g. 1 mm.

FIG. 34 shows another embodiment of a nebulization catheter 576 usedwith an endotracheal tube 580. The endotracheal tube 580 may be aconventional endotracheal tube. The nebulization catheter 576 providesfor a nebulization plume with a reduced forward velocity by imparting aspiral component to the liquid particle flow. The nebulization catheter576 has a distal tip 584 from which a liquid medicine delivered from adistal liquid orifice is nebulized by a flow of pressurized gas from agas orifice located adjacent to the liquid orifice. The nebulizationcatheter 576 is positioned coaxially in the endotracheal tube 580. Acentering device 585 may be used to aid in centering the nebulizationcatheter 576. Located along a portion of the nebulization catheter 576proximal from the tip 584 is a second gas orifice 588. This second gasorifice 588 may open to the same gas lumen that communicates with thenebulizing gas orifice at the distal tip 584 or alternatively, thesecond gas orifice 588 may connect to another, separate gas lumen. Thesecond gas orifice 588 is oriented to direct a pressurized flow of gasin a spiral, distal direction along the distal end of the nebulizationcatheter 576. To accomplish this, the second gas orifice 588 may beformed by an inclined opening or with a deflection foil to direct theflow of gas in the appropriate spiral direction. The spiral flow ofpressurized gas travels along the distal portion of the nebulizingcatheter 576 inside the endotracheal tube 580. The spiral flow of gasentrains the aerosol generated from the distal end 584 of the nebulizingcatheter imparting a spiral flow component to the aerosol plume. Thishas the effect of reducing the forward velocity component of the liquidparticle flow as it leaves the endotracheal tube 580.

FIG. 35 shows an alternative method for using the nebulization catheter576 of FIG. 34. In FIG. 35, the nebulization catheter 576 is shownextended distally of the distal end of the endotracheal tube 580 so thatthe distal portion of the nebulization catheter 576 including the secondgas orifice 588 is located in an airway passage. Taking into account thesize of the airway passage, the nebulization catheter 576 with thesecond gas orifice 588 would operate similarly to the method shown inFIG. 34 and generate a spiral gas flow to reduce the forward velocity ofthe aerosol plume.

Another embodiment of a nebulizing catheter 592 is shown in FIGS. 36 and37. This embodiment of the nebulizing catheter 592 can be used with aseparate endotracheal tube (not shown). The nebulizing catheter 592includes a main shaft 596 having a central lumen 600 and one or moreadditional lumens 604 located around the central lumen 600. In thisembodiment, the central lumen 600 is used for the flow of a pressurizedgas and the additional peripheral lumens 604 are used for the deliveryof the liquid medicine. The lumens 600 and 604 terminate distally inorifices 608 and 612, respectively. Located at a distal end of thenebulizing catheter 592 and immediately adjacent the orifices 608 and612 is a diffuser 616. In one embodiment, the diffuser 616 is composedof a generally disk-shaped body that is sized to deflect the flow of gasfrom the orifice 608 of the central lumen 600 past the liquid orifices612 thereby nebulizing the liquid medicine. A small gap (or venturiarea) 620 between the diffuser 616 and the distal end of the main shaftsection 596 of the catheter 92 provides favorable flow characteristicsfor generating the aerosol. The diffuser 616 may be connected to aretaining wire 624 that is located in the central lumen 600. Theretaining wire 624 may be used to secure the diffuser 616 to the distalend of the nebulizing catheter 592. Also, the retaining wire 624 may beused to pulse the generation of aerosol by reciprocation of thediffuser. It is noted that the aerosol produced by this embodiment has asubstantially radial velocity component and may have only a smallforward velocity component. In addition, a centering device, such aswings 625, may be attached to the diffuser 616.

FIG. 38 shows an alternative embodiment of the diffuser 616. In FIG. 38,the diffuser 616 is formed of a loop that has its ends located in twoapertures in the nebulization catheter shaft tip and a middle portiondirectly in front of the distal gas orifice 608. The loop may be formedof a metal or polymer wire or other material. The loop could be formedby an extrusion method or molded.

Referring to FIG. 39, there is an alternative embodiment of thenebulization catheter system. A nebulization catheter 627 is located inan endotracheal tube 628. The nebulization catheter 627 includes acoaxially arranged outer tube 629, a middle tube 630, and an inner tube631. Liquid delivered through a lumen of the inner tube 631 is nebulizedby pressurized gas delivered in the annular region 632 between the innertube 631 and the middle tube 630. In addition, pressurized gas is alsodelivered from a secondary gas supply that communicates with the annularregion 633 between the middle tube 630 and the outer tube 629. Thesecondary gas supply may be used to help provide the desired plume shapeand velocity. For example, the secondary gas supply delivered from theouter tube 629 can be used to provide a coaxial sheath of air that helpsminimize impaction of the nebulized aerosol on the walls of the tracheaor other airway passage. Alternatively, the secondary air supply may beused to impart additional forward velocity to the aerosol plume. Withthe embodiment of FIG. 39, the additional air flow can be provided bythe secondary gas supply via region 633.

In the embodiments discussed above, nebulization is provided at a distaltip of a catheter by directing a pressurized gas from a distal orificeacross another distal orifice from which the liquid medicine isdelivered. As shown in several of the embodiments above, one way todeliver the liquid from the distal orifice is via a lumen that extendsthrough the catheter to a proximal end. This construction providesefficient operation for many types of medication delivery. In manycases, the distal liquid medicine orifice is subject to a negativepressure due to the pressurized gas flow across it. This negativepressure may in many applications be sufficient to draw the liquid outof the orifice in order to nebulize it. If pulsing of the aerosol isdesired, the pressure of the gas lumen can be pulsed thereby resultingin pulsed generation of the aerosol. By increasing the gas pressure, itmay be possible to also increase the aerosol output.

In other situations, it may be preferable to apply a positive pressureto the liquid, such as at the proximal end of the liquid lumen, in orderto deliver liquid from the distal liquid orifice, it is necessary. Thispositive pressure applied to the liquid lumen may be the same as thatapplied to the gas lumen (e.g. 35-50 psi) or alternatively may bedifferent (less than the gas lumen). If it is desired to pulse thenebulization of the liquid, this can be accomplished by applying pulsesof pressure to the column of liquid via the proximal end of the liquidlumen or reservoir. It may also be preferred to synchronize thepressurization of the gas in the gas lumen with the pressurization ofthe liquid lumen. In addition to applying the positive pressure to theliquid lumen in pulses to generate a pulsed aerosol from the distalorifice, if it may be preferred in an alternative embodiment to apply asmall negative pressure immediately after each positive pressure pulsein order to draw the liquid at the distal orifice back into the liquidlumen to thereby avoid drooling. In a preferred embodiment, the portionof the nebulization catheter in which the liquid lumen is formed may becomposed of a relatively low compliance material to transmit pressurepulses to the distal end with minimum attenuation.

A full length liquid lumen may have disadvantages in certain situations.For example, pulsing of the liquid from the distal orifice may notcorrespond to or follow closely with the application of pressure to theproximal end due to attenuation of the pressure pulse over the length ofthe catheter. In addition, applying pressure to the proximal end of theliquid lumen in order to transmit pressure to discharge the liquid froma distal orifice requires that the lumen be filled with the liquid. Insome situations, this is more medicine than would be required by thepatient and might result in waste.

The embodiment in FIG. 40 addresses these concerns by controlling thepressurization of the liquid as close as possible to the distal liquidorifice, thereby reducing the effects of catheter compliance andattenuation. In FIG. 40, a nebulization catheter 652 has a main body 656having a gas lumen 660 that extends from a proximal end (not shown) to adistal gas orifice 664. The main body 656 also includes a distal liquidmedicine reservoir 668. In the embodiment shown in FIG. 40, the liquidreservoir 668 is located in a distal portion of the main shaft 656 ofthe catheter 652. The liquid reservoir 668 is preferably close to thedistal tip of the nebulizing catheter 652. The liquid reservoir 668 isfilled with the medicine to be delivered. If the amount of medicine issmall in volume, the liquid reservoir may also be correspondingly small.This embodiment is especially suitable for the delivery of small volumesof medicine such as 0.1 to 0.5 ml, e.g. single use. The reservoir 668may be pre-filled during the manufacturing stage of the catheter. Thereservoir 668 may be formed by plugging a lumen of the catheter at adistal location. Alternatively, the liquid reservoir 668 may also extendback to the proximal end of the catheter, thereby forming a liquidlumen, and communicate with a proximal port as described with respect tothe other embodiments discussed herein. This may be required if thelumen is made of a non-compliant material. In yet another alternativeembodiment, the liquid reservoir may be formed in a balloon locatedexternally of the catheter shaft 656.

A filter 672 and plug 676 occupy positions in the distal end of theliquid lumen/reservoir 668. A distal tubular extension 680 extends fromthe plug 676 and communicates with the liquid lumen/reservoir 668. Thetubular extension 680 has a distal orifice 684 aligned with the distalgas orifice 664 so that a pressurized gas exiting the gas orifice 664nebulizes the liquid exiting the liquid orifice 684. The distal liquidorifice may have a sealable cap or wax-like covering associatedtherewith that can be opened when the nebulization catheter is put intouse. In a distal section of the main shaft 656 of the catheter 652, thegas lumen 660 and the liquid lumen 668 are separated by a flexible,distendable wall or membrane 688. In the embodiment of FIG. 40, pulsingof the aerosol is accomplished by pulsing of the gas pressure in the gaslumen 660. When the pressure in the gas lumen 660 is high, it causes theflexible wall 688 between the gas and liquids lumens 660 and 668 todistend into the liquid lumen 668. This is represented by the dashedline in FIG. 40. When this occurs, the pressure from the gas lumen 660is transmitted to the liquid lumen 668 and liquid medicine is forced outthe distal liquid orifice 684. When the pressure applied to the gaslumen 660 is low, the distendable wall 688 recovers its originalposition. It is noted that when the distendable wall 680 recovers itsoriginal position, it may cause a negative pressure at the distal liquidorifice 684 which may cause the liquid to withdraw slightly into thetubular extension 680 thereby reducing the occurrence of liquid droolingat the tip. In addition, it is noted that the delivery of liquid fromthe distal liquid orifice 680 may not occur immediately upon applicationof a high gas pressure to the gas orifice since it will take some timefor the bladder 688 to distend. This means that gas will be flowingsteadily at a high pressure from the distal gas orifice when the liquidbegins to flow from the distal liquid orifice. This also may providecleaner aerosol delivery and reduce the occurrence of drooling of liquidat the tip.

An alternative embodiment of the nebulization catheter 652 shown in FIG.40 may be made using a flexible, but inelastic material for the bladderwall 688. If the bladder wall 688 were flexible, but inelastic, thepressurized gas passing past the liquid orifice 684 would create anegative pressure (venturi effect) thereby drawing out the liquid andnebulizing it. A continuous or preferably an intermittent gas supply tothe venturi area would provide this negative pressure. The bladder wallmay be provided with a vent to facilitate discharge.

In order to manufacture a nebulization catheter with compliant andnon-compliant regions, as described above, the catheter may beco-extruded using different compounds or polymers to optimize thephysical properties of the different wall sections. It may be preferredto use high energy radiation to crosslink the polymer material in theformation of the bladder wall.

V. Alignment of the Aerosol Plume

The embodiments described above are directed to developing an optimumnebulization plume. It is further recognized that another factor thatcontributes to the efficiency of the nebulization is the position of thenebulization catheter relative to the anatomical environment. Forexample, even if the nebulization catheter being used develops anoptimal plume, the delivery efficiency of the catheter may besignificantly impaired if the plume is directed into the wall of theendotracheal tube, the trachea or other airway passage. Accordingly,proper location, orientation, and alignment of the nebulization catheterin the anatomy can be an important factor contributing the delivery ofmedicine via a nebulization catheter. In general, it is preferable toalign the catheter coaxially in the airway passage in which it islocated.

It is also noted that an endotracheal tube, if present, can adverselyeffect delivery of aerosol from a separate nebulization catheter. Forexample, an endotracheal tube has an inner diameter that is smaller thanthe diameter of the trachea so that if the nebulization takes placeinside the endotracheal tube, a portion of the aerosol may impact theinner wall of the endotracheal tube and thereby be wasted. Mostconventional endotracheal tubes have a curved distal end that isrelatively rigid so that when it is in place in the trachea of apatient, the distal end of the endotracheal tube is oriented off center.This can affect the orientation of a nebulization catheter located inthe endotracheal tube causing it direct its aerosol into the tracheawall even if the nebulization catheter is positioned so that its distalend is located distally of the endotracheal tube. In general, it isdesirable to allow the aerosol particles to avoid impaction for severalcentimeters after the aerosol is produced so that the aerosol particlescan lose their velocity and become entrained in the inspiratory airflow.

The embodiment of the invention in FIG. 41 is directed at providingimproved alignment of a nebulization catheter in a patient's trachea. InFIG. 41, an endotracheal tube 700 is positioned in a trachea 704 of apatient. The endotracheal tube 700 is of a type that has an inflatablecuff 708 located around a distal exterior side to facilitate positioningand alignment of the endotracheal tube 700 in the trachea 696. Extendingthrough and out of a distal end of the endotracheal tube 700 is anebulization catheter 712. The nebulization catheter 712 may be similarto any of the embodiments of the nebulization catheter described above.Located around a distal portion 716 of the nebulization catheter 712 isa spring centering apparatus 720. The spring centering apparatus 720includes a retainer ring 724 fixed to the shaft of the nebulizationcatheter 712 and a plurality of arms 728 connected to the ring 724. Inone embodiment, there are three arms 726. The arms 726 are flexible andresilient. The arms 726 may be made of a spring tempered metal or asuitable plastic. Located at the end of each of the arms 726 oppositeits connection to the ring 724 is a ball 727. The spring centeringapparatus 720 is deployed by first positioning the nebulizing catheter712 including the spring centering apparatus in the lumen 728 of theendotracheal tube 700. The arms 726 are formed so that they assume asize larger than the diameter of the trachea or airway passage.Accordingly, when the centering device is positioned in the endotrachealtube 700, the arms are resiliently deformed into a compressedconfiguration with the balls 727 close to the shaft of the nebulizingcatheter 712. To deploy the centering device, the nebulizing catheter712 is advanced out the distal end of the endotracheal tube 700. Whenthe balls 727 are advanced out the endotracheal tube 700, they springout to an expanded size and engage the walls of the trachea or otherairway passage. The balls 727 provide a relatively smooth surface tolimit irritation or injury to the trachea walls or other airway passage.With the arms expanded, the nebulizing catheter is centered in thetrachea or other airway passage so that a plume discharged from a distalend of the nebulizing catheter has minimal contact with the walls of thetrachea or other airway passage. When it is necessary to remove thenebulizing catheter 712, it can be withdrawn in a proximal directionback into the endotracheal tube 700. In a preferred embodiment, the armsare formed of a thin resilient wire or polymer, preferably less thanapproximately .015 inches in diameter. The arms and/or the balls may bemade of, or coated with, a radiopaque material. It is an advantage ofthe embodiment of the centering device shown in FIG. 41 that it islocated somewhat in advance of the distal end of the nebulizationcatheter. This positions the arms 726 of the centering device in theportion of the trachea or other airway passage into which the aerosolwill be initially flowing. Thus, the centering device orients the distaltip of the nebulization catheter relative to the portion of the tracheaor other airway passage beyond the distal tip thereby helping to reduceimpaction along this portion.

FIG. 42 shows an alternative embodiment of the nebulization catheter. Anebulization catheter 729 is used with an endotracheal tube as describedabove. The nebulization catheter 729 includes a centering device 730.The centering device 730 includes a plurality of arms 731 that areformed to resiliently extend outward from the axis of the catheter shaftto engage the wall of the patient's trachea or airway passage or theinterior of an endotracheal tube depending upon the desired location ofthe distal end of the nebulization catheter. At the ends of each of thearms 731 are balls 732. The proximal ends of the arms 731 are formed ofwires 733 that extend through lumens 734 in the shaft of the catheter729. Each of the lumens 734 has a distal opening 735 from which an armcan extend. The distal openings are approximately 0.10-1 cm from thedistal end of the catheter shaft. The proximal ends of the wires 733exit the lumens 734 of the nebulization catheter via openings 736 thatare close to the proximal end of the catheter in a portion of thecatheter that would normally be outside the patient's body during use.Thus, the proximal ends of the wires 733 are accessible to the physicianduring use. By pulling and pushing on the proximal ends of the wires733, the portion of the arms 731 that extend from the openings 735 canbe adjusted. Thus, the arms 731 can be adjusted from a fully retractedto a fully advanced position by pulling or pushing on the proximal endsof the wires 733. In addition, since the proximal ends can of the wires733 be adjusted in any intermediate position between the fully retractedand fully advanced positions, the physician can adjust the size of thecentering device 730 to any appropriate size, as desired. Because thewires 733 should assume a desired shape when advanced out of the lumensin which they are contained during positioning, it is preferable thatthey be formed of a material that has shape memory properties so thatthe desired expanded shape can be imparted to the wires duringmanufacture. In one embodiment, the wires may be formed of nitinol.

In one preferred embodiment, a second centering device 737 is alsoprovided. The second centering device 737 is located on the shaft of thenebulization catheter 729 proximally from the first centering device730. The second centering device 737 may be formed of resilient wingsformed of a material such as plastic or metal that extend radiallyoutward from the shaft. The second (or proximal) centering device 737helps keep the distal portion of the catheter 729 in alignment.

FIG. 43 shows another alternative embodiment of the present invention. Anebulizing catheter 738 is shown which may be similar to the catheter 20of FIG. 1. The nebulizing catheter 738 includes a centering device 739.The centering device 739 includes a wire loop 740 located at a distalend of the catheter. One end 741 of the loop 740 connects to the distalend of the nebulizing catheter shaft. The other end 742 of the wire loop740 enters an opening 743 in the shaft that communicates with a lumen744 that extends to a proximal end of the catheter 738. A proximal end745 of the wire exits the lumen 744 via an opening 746 in a proximalportion of the nebulizing catheter which is normally outside thepatient's body during use. The size of the wire loop 740 can be adjustedby advancing or withdrawing the proximal end 745 of the wire. In thisembodiment, it can be determined that the centering device is fullyretracted when the wire 745 cannot be withdrawn any further. Theposition of the distal end of the nebulization catheter can also bedetermined by the resistance to further retraction caused when the loopsor arms engage the distal end of the endotracheal tube. When in anexpanded size, the wire loop 740 engages the walls of the trachea orairway passage or the interior of the endotracheal tube depending uponwhere the distal end of the nebulizing catheter is positioned. The sizeof the wire loop 740 can be adjusted from a fully reduced size to afully expanded size as well as intermediate sizes. With the embodimentof FIG. 43, the size of the loop can be adjusted to different sizeairway passages in different patients or alternatively the size of theloops can be adjusted to different airway passages in the same patientif the physician desires relocating the nebulizing catheter to differentlocations in a patient's respiratory tract. In a one preferredembodiment, more than one wire loop may be provided at the distal end ofthe nebulizing catheter. It is noted that the wire loop 740 of thisembodiment may also be used in for facilitating positioning over a guidewire in a manner similar to loop 106 shown in FIG. 9.

FIGS. 44 and 45 show another alternative embodiment of the presentinvention. A nebulizing catheter 747 has a shaft portion 748 and a wireloop 749 extending from a distal end of the shaft 748. In thisembodiment, the wire loop 749 is connected at each end 750 and 751 tothe distal end of the catheter shaft 748. A retractable sheath 752 ispositioned over the nebulizing catheter shaft 748. The sheath 752 can beadvanced and withdrawn relative to the catheter shaft 748. When it isdesired to maneuver the nebulizing catheter into a desired position inthe respiratory tract of a patient, the sheath 752 is advanced over theloop 749 to maintain a low profile, as shown in FIG. 45. When the distalend of the nebulizing catheter is suitably positioned, the sheath 752 isthen retracted, as shown in FIG. 44, allowing the loop 749 to expand toits expanded size to center and align the distal end of the nebulizingcatheter in the respiratory tract. In one embodiment, the loop 749 isformed of a superelastic material such as nitinol.

As noted above, proper positioning and alignment of the nebulizationcatheter can be an important factor affecting drug delivery efficiency.In general, it is preferable to position the tip of the nebulizingcatheter as closely to the central region of the trachea (or otherrespiratory passage, such as the bronchi) as possible. It is furthernoted that even if the catheter can be centered relative to the trachea,if a section proximal to a centering device is misaligned, it can affectthe directional orientation of the tip. This situation is represented inFIG. 46 in which a nebulizing catheter 753 is centered, but the tip isnot properly aimed to provide an optimum plume. This potential problemcan be overcome by using an embodiment of the invention shown in FIG.47. In FIG. 47, a nebulizing catheter 754 is located in a trachea 755 ofa patient. The nebulizing catheter 754 extends out the end of anendotracheal tube 756. A first centering apparatus 757 is located on amain shaft 760 of the nebulizing catheter 754 close to the distal end764. The first centering device 757 may be similar to the centeringdevices shown in FIGS. 41-45. A second centering device 768 is locatedaxially along the nebulizing catheter shaft 760 proximally from thefirst centering device 757. The second centering device 768 may be thesame as the first centering device 757. As shown in FIG. 47, the twocentering devices 757 and 768 not only serve to position thenebulization catheter 7754 centrally in the trachea, but also serve toalign the nebulizing catheter tip to expel the plume along a centralaxis of the trachea.

The proximal centering device 768 may be substituted by another type ofcentering device or may employ the endotracheal tube 756 for thispurpose, as shown in FIG. 48. If the endotracheal tube is used to assistin centering the nebulization catheter, it may incorporate a distal,elongated occlusion cuff 772 or balloon to coaxially align it accuratelyin the trachea. Most conventional endotracheal tubes are provided with acurvature to facilitate positioning the trachea of a patient. Inaddition, most conventional endotracheal tubes are relatively stiff.These factors may result in the misalignment of the distal end of theendotracheal tube relative to a patient's trachea as illustrated inFIGS. 46 and 47. In order to use the endotracheal tube for centering ofthe nebulization catheter, it is preferable to make the tip of theendotracheal tube straighter and/or more flexible than in conventionalendotracheal tubes to ensure proper concentricity with the occlusionballoon and the trachea. An endotracheal tube with a straighter and moreflexible tip is shown in FIG. 48. In addition, the endotracheal tube maybe provided with a centering or aiming device 776 for aligning thenebulization catheter 754. In the embodiment of FIG. 48, the aimingdevice 776 is formed by a plurality of flexible or resilient wings theextend from the wall of the endotracheal tube 756 toward an axiallycentral position.

Appropriate centering and aiming of the nebulization catheter can beaffected by anatomical factors. It is noted that in some circumstances,it is preferable to position the distal tip of the nebulization catheterinto either bronchus of the lungs or even into separate bronchia.Positioning of the nebulizing tip closer to the alveoli may enhance drugdelivery efficiency. In a situation in which it is desired to place thenebulizer tip in both bronchi of the lungs, a nebulizing catheter 780with dual tips can be employed, as shown in FIG. 49. When using a dualtip catheter such as shown in FIG. 49, centering and aiming can beimportant considerations because of the narrower air passages in each ofthe bronchi. To provide for centering and aiming of a dual tipnebulizing catheter, each of the tips 784 and 788 may be provided withits own centering apparatus, such as 792 and 796. These centeringdevices may be similar to the centering devices described above.Alternatively, the centering devices 792 and 796 may be formed of armsor struts, made of a flexible or resilient material, that bow out fromthe shafts of each of the tips 784 and 788, as shown. These struts maybe formed with a shorter length in order to fit into smaller airwaypassages or alternatively they may be made to provide a range ofdeployment sizes to accommodate different airway passages.

As an alternative to providing a nebulizing catheter with dual tips 784and 788 as shown in FIG. 49, if delivery of aerosolized medicine intoseparate branches of the lungs is desired, it may be preferred to use anebulizing catheter with a single nozzle tip that has multiple orificesor jets aimed toward the desired branches.

With respect to all the centering devices described above, it is notedthat some aerosol may impact the wires or loops that form the centeringdevices and accordingly, the centering devices are preferablyconstructed of wires or other materials having a small diameter or crosssection to minimize losses due to such impaction. Moreover, the overallimproved efficiency due to the reduction in aerosol impaction on thewalls of the trachea or other airway passage is expected to more thancompensate for amy losses due to impaction on the centering device.

Another alternative means for centering the distal end of a nebulizationcatheter in the air passage is to use part of the pressurized gas for apneumatic centering device. Air jets generated from two or more outwarddirected orifices spaced evenly around the outer circumference of thenebulizing catheter near the tip can be used to center the catheter inthe airway. This alternative may help avoid irritation and provideadditional advantages compared to physical centering devices.

Another alternative way to help center the nebulizing catheter in thepatient's airway passage is to use a balloon or wire centering deviceplaced near the nebulizing catheter tip. The balloon or wire centeringdevice can be temporarily inflated to double check the placement of thenebulizing catheter tip in relation to the endotracheal tube tip. To usethis feature the nebulizing catheter is advanced beyond the endotrachealtube tip using markings on the proximal shaft to judge the distance. Thecentering device or balloon would then be expanded to a diameter largerthan the endotracheal tube and the catheter retracted until thecentering device or balloon could be felt engaging with the endotrachealtube tip or until the endotracheal airflow was obstructed.

VI. Operation and Flow Control

As mentioned above, the driving gas used to pressurize the gas lumen maybe pure (e.g. 100%) oxygen at a pressure of 35-50 psi. Other gases andpressures may be used with suitable adjustments to provide for thedesired particle size. The pressurized gas also may be humidified by abubbler or other suitable means and warmed, if necessary.

Regarding the liquid lumen, one way to deliver the liquid drug throughthe nebulizing catheter is by a manually operated syringe. To delivery aliquid drug in this manner, a syringe containing the liquid medicine tobe nebulized is connected to the liquid port on the manifold connectedto a proximal end of the nebulizing catheter. Then, the liquid isinjected while the pressuring gas is being supplied to the nebulizingcatheter via the gas inlet port on the nebulizing catheter manifold.Using a manually operated syringe is reliable, easy to use, and may bepreferred when it is desired to deliver only a small amount ofmedication.

In a preferred embodiment, the liquid drug is delivered to thenebulizing catheter from a pressurized source. A pressurized source forthe liquid medicine can provide for a generally higher and more uniformpressure. A high pressure assists in clearing any blockages that mayocclude the liquid lumen. Pressurization of the liquid lumen also canensure that all the liquid drug is evacuated from the catheter tip. Inaddition, use of a liquid pressurization source can provide for drugdelivery for a longer period of time or a drug delivery that is timed orpulsed to coincide with operation of a ventilator, if used. In apreferred embodiment, the same pressure source (at 50 psi) that is usedto provide the gas pressurization can also be used to provide forpressurization of the liquid. Some ventilators have an auxiliary portthat are used for externally located nebulizers. The pressure flow fromthis auxiliary port may be used as a pressure source to drive the liquidand gas supplies of the embodiments of the nebulizing catheterconsidered herein. Alternatively, a sensor located in the flow from thisauxiliary port may be used to trigger another control device thatoperates the pressurized liquid and gas supplies.

In a preferred embodiment, the generation of the aerosol can besynchronized with the inhalation of the patient. In one embodiment, thiscan be accomplished with a manually operable control gas valve on thegas pressure line to the liquid input port. This may be suitable whenthe medicine can be delivered in a short period of time, e.g. a fewrespiratory cycles. Alternatively, when it is preferred to deliver themedicine for an extended period of time, it may be preferred to employ asystem that can automatically deliver medicine via the nebulizer from asource of liquid medicine. In such a system, the gas and/or liquid floware triggered by the patient's respiratory cycle with the use of anelectronic pressure sensor and relay actuator.

An important factor relating to effective delivery of medication via anebulizing catheter is the flow control system for pressurizing andsupplying the gas and liquid to the proximal end of the nebulizationcatheter. In many circumstances, it is envisioned that medication willbe delivered to the patient via a nebulization catheter that is in placein the patient over an extended period of time, such as several hours ordays. In such circumstances, it would be preferred to use a system thatautomatically delivers the proper dosage of medication from a supply ofthe medicine to the patient at the proper rate, and further that canoperate automatically and unattended. Further, it would be preferred toprovide a means to detect when the supply is running low so that eitherthe nebulization catheter can be disconnected or a new supply provided.FIGS. 50 and 51 show several embodiments of a reservoir andpressurization system for use with a nebulizing catheter.

Referring to FIG. 50, a reservoir and pressurization assembly 800 isconnected to a proximal end of a nebulization catheter. The nebulizationcatheter may be similar to any of the embodiments described above. Theassembly 800 has a gas inlet port 804 that can connect to an externalpressurized gas supply. The external pressurized gas supply may be themain gas supply of the hospital or may be provided by another unit. Theexternal gas supply may provide oxygen at 50 psi. The gas inlet port 804communicates with an airflow passageway 808 defined by and extendingthrough the assembly 800. The assembly 800 includes a gas output port812 that communicates with the fluid flow passageway 808 and whichconnects to a gas inlet port of the nebulization catheter (not shown).The gas output port 812 is located immediately downstream of the gasinlet port 804. Located in the fluid flow passageway 808 downstream ofthe gas outlet port 812 is a filter 816. The filter 816 is preferably ahydrophobic filter that allows the passage of gas but which wouldprevent the backflow of any liquid. Located downstream of the filter 816in the fluid flow passageway 808 is an injection port and reservoir 820.This port 820 communicates with a supply of the liquid fluid medicationto be supplied to the nebulizing catheter. Located next in the fluidflow passageway 808 is a capillary tube drug reservoir 824. Thecapillary tube reservoir 824 is comprised of a length of plastic tubingadapted to hold a supply of the liquid medication to be delivered. Inthe embodiment shown, the capillary tube reservoir consists of a helicalcoil of transparent tubing. Located downstream of the capillary tubingreservoir 824 is a liquid outlet 828 that connects to a liquid inletport of the nebulization catheter (not shown). With the embodiment shownin FIG. 50, the transparent capillary tubing 824 provides a convenientand reliable way to ascertain the supply of medication to the nebulizingcatheter. The capillary tubing because of its length is capable ofcontaining a suitable supply of the medication. When the attendingmedical personnel observe that the medication is about to run out, a newsupply can be readily provided. The clear capillary tube allows easyvisualization of the drug flow by watching the gas-drug meniscus traveldown the tube. Instead of relying on direct observation by medicalpersonnel, the capillary tubing may be used with an automatic detectiondevice, e.g. a photocell, that provides an alarm to the medicalpersonnel upon detection that the medication is running out in thecapillary tubing or that the meniscus has ceased moving due to ablockage. A blockage may also be detected by detection of an increase inpressure.

FIGS. 51 and 52 show another embodiment of a fluid reservoir andpressurization assembly 832. This embodiment includes a gas inlet 836, afluid flow passageway 840, a liquid medicine supply vent 844, a filter848, a capillary channel section 852, and an outlet port 856. In thisembodiment, the filter 848 is located downstream of the filling vent844. The filter 848 allows the pressurized gas to push the liquid drugduring use but prevents the liquid drug from backing up to the ventduring filling. In this embodiment, a second injection port 860 isprovided downstream of the capillary section 852 and a second filter 864is located downstream of the second injection port 860. The secondfilter 864 is preferably a filter having approximately a 20 μmretention. Also, in this embodiment, the capillary section 852 may becomposed of a planar section 865. The planar section 865 may be a pieceof plastic having a winding channel molded, routed or otherwise formedtherein. The planar section 868 is preferably colored to providesuitable contrast with the liquid solution flowing therethrough. Atransparent flat plastic cover is positioned over the winding channel ofthe planar section 865 to form the closed channel of the capillarysection. The fluid channel in the capillary section preferably has anI.D. of approximately 2 mm. The second inlet port 864 provides anadditional means to add medication to the nebulizing catheter liquidflow. When the capillary channel in the section 852 has been filled, thegas is used to pressurize the tube and force the fluid to the cathetertip. The second filter 864 acts as a restrictive orifice to preciselymeter the flow to the nebulizing catheter. The clear capillary channelallows easy visualization of the drug flow by watching the gas-drugmeniscus travel down the tube. The narrow tube makes the flow appear tomove quickly even at slow delivery rates. Thus, any flow interruptioncan be easily observed. The capillary tubing section also ensures thatalmost 100% of the drug is delivered to the catheter tip since there isno dead space in the line except at the injection port 860.

During ventilation of a patient with an endotracheal tube, especiallywhen intubation that takes place for a long period of time, it isconsidered desirable to humidify the air being delivered. When anebulization catheter is used for delivery of medicine, either inconjunction with an endotracheal tube or even without an endotrachealtube, it is possible to utilize the nebulization catheter for providinghumidification in addition to medicine delivery. An embodiment of a flowdelivery system for a nebulizing catheter incorporating humidificationis shown in FIG. 53. A suitably large reservoir 866 holds sterile wateror saline. The reservoir 866 is connected to the liquid supply lumen 867of a nebulization catheter 868. Solution is drawn into the nebulizationcatheter 868 from the reservoir 866 by negative pressure at the cathetertip, gravity, a pump in the solution supply line distal of thereservoir, or by pressurizing the reservoir by a suitable means.

Medicine may be added to the humidification water in at the followingways. In a first alternative, the medicine is added to the isotonicsaline in the solution reservoir 866 thereby providing for high dilutionand slow, continuous delivery of the medicine along with the water. Insecond alternative, the medicine is introduced into the solution supplyline 867 via an injection port 869 between the reservoir 866 and theliquid lumen of the catheter 868. The medicine may be delivered to theinjection port of the solution supply line from a solution reservoirsystem such as system 800 of FIG. 50. Using this latter alternative, amore concentrated dose of the medicine can be delivered at the specifictime preferred by the physician. It may also be preferable to include amolecular sieve, check valve or air trap 870 between the reservoir 866and the injection port to the to ensure that the medicine cannot flow ordiffuse backwards into the reservoir 866.

When delivering medicine to the lungs or when delivering water forhumidification, it may be desired to heat the liquid prior to delivery.This may especially be appropriate since expanding gases which areassociated with the nebulization of liquids may remove heat from thebody. In order to address this concern, a heating element 871 may beassociated with the liquid supply line 867 to the nebulizing catheter868. This heating element 871 may include an electric coil wound aroundthe supply line 867 or may use a heated water flow in a tubing woundaround the supply line 867. The heating element 871 may be used inembodiments that provide for humidification as well as those that donot. Alternatively, the heating element 871 may be associated with thegas supply line or with the liquid reservoir 866.

It is generally considered preferable to operate the nebulizing catheterso as to generate an aerosol that is carried by a patient's inhalationto the lungs. This requires a pulsing of the aerosol generation so thatit is timed to coincide with the inhalation of the patient. If thepatient is intubated, the timing of the nebulization can be synchronizedwith the operation of the ventilator. It is recognized that it may bepreferable to begin the nebulization slightly in advance of, at, orslightly after, the beginning of the inhalation period in order toaccount for the distance between the nebulization tip and the alveoli.Also, it may be preferable to stop the nebulization slightly before theend of the inhalation period in order to avoid wasting aerosol after theinhalation flow has stopped.

This continuous pulsing of the aerosol can be accomplished by a system872 as shown in FIGS. 54 and 55. FIGS. 54 and 55 show a portion of theflow control system for a nebulizing catheter. A flow line 876 has aninlet 880 and an outlet 884. The flow line 876 may be formed of a soft(e.g. compliant) tube. The inlet 880 connects to the source of liquidmedicine and in particular may attach to the liquid outlet (828 or 856)of the liquid reservoirs shown in FIGS. 50-52. The flow line outlet 884in FIGS. 54 and 55 connects to the liquid inlet port on the manifold ofthe nebulizing catheter, such as port 32 in FIGS. 1 and 2. Locatedaround a portion of the flow line 876 is an actuator piston 888. Theactuator piston 888 includes a solenoid pinch valve 892 that can impingeupon the portion of the liquid flow line 876 extending therethroughthereby pinching it off. The actuator piston 888 is connected to andoperated by a controller that receives input from the ventilator (suchas from the auxiliary port used for an external nebulizer) so that theactuator piston 888 is operated to open and close the flow linesynchronous with the inhalation and exhalation phases of the ventilator.Instead of a solenoid piston, a metering valve or reversible syringepump may be used.

In a preferred embodiment, the flow control system 872 uses a dualsolenoid arrangement to provide a draw-back feature. Pulsing of theliquid flow by actuation of the actuator piston 888 may result in someliquid being left at the distal nebulizer liquid orifice when thepressure is turned off. This may result in small amounts of liquiddrooling from the distal liquid orifice tip since the liquid is notbeing expelled under controlled pressure conditions. In order to limitthe occurrence of such drooling, a draw back feature is provided in theflow control system. The draw back feature is provided by a secondsolenoid 896 which is associated with a bladder 900 that communicateswith the flow line 876. The bladder 900 communicates with the flowcontrol line 876 downstream of the actuator piston 888. A small amountof fluid (liquid/air) occupies the bladder 900. The bladder is composedof an elastic material that is formed with a tendency to recover to anexpanded size. When the actuator piston 888 opens to allow the flow offluid to the distal end of the nebulizing catheter, the second solenoid896 moves to a closed position thereby compressing the bladder 900 andsqueezing fluid out of it into the fluid flow line 876, as shown in FIG.54. During the exhalation stage of the ventilation cycle, the actuatorpiston 888 closes to shut off the flow of fluid to the distal end of thenebulizing catheter. When the actuator piston 888 closes, the secondsolenoid 896 opens, as shown in FIG. 55. This allows the bladder 900 toresiliently recover to its expanded size, and when it does, it drawsfluid into it from the fluid flow line 876. Because the fluid flow line876 is closed proximally at the actuator piston 888, when the bladderdraws fluid into it from the fluid flow line 876, it draws fluid fromthe distal end of the fluid flow line that connects to the nebulizingcatheter liquid lumen. This causes the entire column of liquid in theliquid lumen of the nebulizing catheter to move slightly in a reversedirection (i.e. proximally) thereby moving the liquid away from thedistal orifice. In this manner, the flow control system of FIGS. 54 and55 allows the draw back of liquid in the flow line in a reversedirection during the exhalation phase of the ventilator when the liquidflow line is shut off.

VII. Selective Nebulization Therapy Delivery

When delivering medication with a nebulizing catheter, it may bedesirable to deliver the medication to only one of the bronchi of thelungs and not the other or to only certain bronchia and not others. Areason for this type of selective therapy may be that only one area ofthe lungs requires medication. An embodiment of the invention shown inFIG. 56 facilitates selective delivery of a medication via a nebulizingcatheter to only one bronchus. In FIG. 56, an endotracheal tube 904 ispositioned in a trachea 908 of a patient. A nebulizing catheter 912 ispositioned in the endotracheal tube 904. This nebulizing catheter 904may be similar to the embodiments described above. This nebulizingcatheter 904 may even be of the type that is non-removably incorporatedinto the endotracheal tube. A second catheter 916 extends distally ofthe endotracheal tube 904. The second catheter 916 may be positioned inthe ventilation lumen 920 of the endotracheal tube 904. The secondcatheter 916 includes a lumen through which a low flow pressurized gascan be conveyed. A proximal end of the second catheter 916 extends outof the proximal end of the endotracheal tube 904 through a suitablefitting, such as the fitting described in U.S. Pat. No. 5,078,131(Foley). A suitable source of pressurized gas is attached to a proximalend of the second catheter 916. This gas source may be the same gassource used for the pressurized gas lumen of the nebulization catheter912. A distal end 928 of the second catheter 916 is positioned in thebronchus 932 other than the bronchus to which it is desired to delivernebulized medication. Pressurized gas is delivered through the secondcatheter 916 out an orifice 936 in the distal end thereof. The deliveryof pressurized gas out the distal end 936 of the second catheter 916causes the pressure level in the bronchus 932 to be slightly greaterthan in the other bronchus. Accordingly, when the nebulizing catheter912 generates an aerosol of liquid medicine, it will tend to flow withthe inhalation stream from the endotracheal tube 904 to the bronchusother than the one with the second catheter 916. In this manner, one ofthe bronchi of the lungs, or even selected bronchia, can be selectivelymedicated using a single nebulization catheter positioned in theendotracheal tube.

VIII. Timing of Nebulization

As mentioned before, in order to deliver the nebulized medicine to thelungs, it is preferred that the medicine is carried by the inhalation ofthe patient. A number of factors affect the efficiency of the medicinedelivered this way. The following embodiments are directed to improvingdrug delivery efficiency taking into account some of these factors.

If the patient is intubated, it may be possible to synchronize thetiming of the nebulization pulse with the patient's ventilation. In oneembodiment, this may be accomplished by providing an interface betweenthe ventilator and the nebulizer. In some circumstances it may bepreferred to provide other means for triggering the nebulization. Forexample, the ventilator being used may not provide a suitable interface.Also, the ventilator may not provide sufficiently accurate informationconcerning the patient's respiration to enable the nebulization catheterto operate with highest efficiency. In such situations, it may bepreferred to utilize one or more separate sensors to obtain informationthat can be used to trigger and operate the nebulization catheter.

Referring to FIG. 57, there is a nebulizing catheter 944 positioned inan endotracheal tube 948 located in the trachea 952 of a patient. Aproximal end of the endotracheal tube 948 is connected to a ventilator956. In order to obtain physiological information concerning thepatient's respiration for use in timing the generation of nebulizationpulses by the nebulization catheter 944, one or more sensors may beused. For example, a first sensor 960 may be located on a distal end ofthe endotracheal tube 948. In addition, a sensor 964 may be positionedon the nebulization catheter 944. Another sensor 968 may be positionedon a separate device, such as a separate catheter 972 which is locatedfurther distally in the respiratory system. In addition, a sensor 976may be positioned in the ventilator circuit of the ventilator 956 or ina ventilator auxiliary port, if available, or elsewhere on the patient.These sensors 960, 964, 968, and 976 may be types of sensors thatmeasure pressure, flow or a physiological parameter of the patient, suchas muscle contraction, electophysiological activity, etc. In alternativeembodiments, one or more of these sensors may be used.

FIGS. 58 and 59 show alternative embodiments of nebulization cathetersthat incorporate sensors. In FIG. 58, a nebulization catheter 980 isshown. This nebulization catheter 980 may be similar to the nebulizationcatheter in FIG. 11. In FIG. 58, a main shaft 984 includes a pluralityof lumens with a centrally located lumen 988 used to deliver a liquidmedicine and a plurality of lumens 992 located peripherally around itused to deliver a pressurized gas. One of the peripheral lumens 996 isnot used for pressurized gas delivery, but instead is used for sensingpurposes. This may be accomplished by forming an aperture 1000 through awall of the main shaft 984. The aperture communicates with the sensinglumen 996. The aperture 1000 may be open or may be covered with aflexible diaphragm that permits transmission of pressure across it. Apressure sensing device may be located at a proximal end of thenebulizing catheter. The pressure at the distal end of the nebulizingcatheter can be sensed by the proximally located sensing device via thesensing lumen 996. This could rely on pneumatic sensing of the distalair pressure. Because of the effect of the distal gas pressurizationorifice, pressure sensing through the sensing lumen 996 may be used forpurposes of gross overpressure for safety purposes. Alternatively, thepressure sensing lumen 996 may be used during periods of time when apressurizing gas is not being delivered to sense the patient'sphysiological airway pressure.

FIG. 59 shows another embodiment of a pressure sensing nebulizationcatheter. This embodiment is similar to the embodiment of FIG. 58 exceptthat a sensor 1004 is located at a distal end of the catheter 980,specifically in the aperture 1000. In this embodiment, the sensor 1004is a pressure transducer. Wire leads 1008 extend proximally from thesensor 1004 via the lumen 996. Instead of measuring pressure, the sensor1004 could measure the flow at the distal end of the catheter. This maybe accomplished by piezoelectric, optical, Hall effect, or other typesof sensor technologies. The sensor may also be of a fiber optic type.

Although the embodiments of FIGS. 58 and 59 show sensing apparatusesassociated with a nebulization catheter, these same types of sensorscould also be used in the endotracheal tube 948, the separate catheter972, or the ventilator 956 of FIG. 57 or the ventilator circuit.

The sensor outputs information to a controller 1012 that operates theflow control portion 1013 of the nebulization catheter system. The flowcontrol portion may include the flow control assembly 872 (shown in FIG.55) as well as include the control functions for gas pressurization. Thecontroller 1012 may have preset triggering parameters or may be useradjustable. The controller 1012 may use airway flow, pressure, orphysiological activity as a basis for controlling the flow controlassembly 1013. The controller 1012 may provide for pulsing based uponany one of the following modes: (1) a controlled volume (bolus) ofmedicine is delivered with each pulse; (2) medicine is delivered until aphysiological condition is sensed, e.g. exhalation; or (3) medicine isdelivered for a fixable time interval, e.g. 2 seconds. These modes ofoperation may be selectable by the physician based upon the preferredtreatment taking into account the patient's condition, the type ofmedicine being delivered, etc.

It may also be desired to regulate the delivery of aerosol so that it isnot delivered with every inhalation. As mentioned above, one concernwith delivery of an expanding gas is the cooling effect that it may haveon the body. This can be a factor with high gas flow rates. Accordingly,it may be preferable to deliver aerosol on every other inhalation orevery third inhalation, and so on. Alternatively, it may be preferred todeliver aerosol for certain periods of time, e.g. 5 minutes every hour.Therefore, by alternating aerosol delivery, the cooling effectassociated with it can be reduced.

IX. Alternative Embodiments

A. Nebulizing Catheter Incorporated in Endotracheal Tube

The various embodiments of nebulizing catheters, disclosed above, havebeen described as being either adapted for use in conjunction with aseparate endotracheal tube, or adapted to be used without anendotracheal tube. If used with an endotracheal tube, the embodiments ofthe nebulizing catheter disclosed above are preferably removable fromthe endotracheal tube if one is present. It is noted that many of theembodiments of the present invention disclosed herein may also be usedin conjunction with a nebulization catheter that is non-removable froman endotracheal tube, i.e. in which the nebulizing catheter isincorporated into and forms part of the endotracheal tube. Anendotracheal tube that provides for nebulized medication delivery isdescribed in a patent application filed by Dr. Neil R. MacIntyre onMarch 10, 1992 entitled "Endotracheal Tube Adapted for AerosolGeneration at Distal End Thereof", the entire disclosure of which isincorporated herein by reference. According to a system developed by Dr.MacIntyre, there is provided an endotracheal tube that provides fornebulization of a medication at a distal end thereof. According to Dr.MacIntryre's system, an endotracheal tube includes two additional,separate lumens, in addition to its main ventilation lumen used for thepatient's breathing airflow. A medication in a liquid form is conveyedthrough one of the additional lumens and a pressurized gas is conveyedthrough the other lumen. The two additional lumens have distal openingsnear the distal end of the endotracheal tube airflow lumen. The distalopening of the pressurized gas lumen directs the pressurized gas acrossthe distal medication lumen opening thereby nebulizing the liquidmedication so that it can be delivered to the patient's lungs. It isintended that the present invention covers embodiments of nebulizationcatheters that are non-removable relative to an endotracheal tube.

B. Aerosol Generation with Porous Material

FIG. 60 shows another catheter 1060 for producing an aerosol. Thecatheter 1060 generates an aerosol, or aerosol-like plume by use of aporous material or sponge located in a lumen of the catheter. Thecatheter 1060 has a main shaft 1064 with a lumen 1068 through whichliquid medicine is conveyed under pressure and a lumen 1072 throughwhich a gas is conveyed under pressure. A porous material 1076 islocated in a distal end of the shaft 1064 so that both lumens 1068 and1072 convey their contents into the porous material 1076. The porousmaterial 1076 may be a porous polyethylene made by Porex. Alternatively,the porous material may be a polymer sponge or other polymer material.Located in the main shaft 1064 distal of the porous 1076 is an end cap1080 with an orifice 1084 located therein. The orifice is small andmaintains a positive back pressure in the catheter shaft and porousmaterial area. The end cap 1080 is separated from the distal side of theporous material 1076 by a small gap 1082. The liquid and gas deliveredunder pressure to the porous material 1076 migrate through the porousacross the gap 1082 toward the aperture 1084. The liquid and gas becomeintermixed under pressure and as they are expelled from the fine tiporifice the gas expands and disperses the liquid particles into finedroplets. Upon discharging through the aperture 1084, the medicine formstiny droplets, e.g. an aerosol. The aerosol is conveyed to the lungs ofthe patient in a manner similar to that described in the embodimentsabove. An advantage of using a porous material or sponge at the distalliquid orifice is that it reduces drooling of the liquid.

C. Secondary Aerosol Generation

In some situations it may be desirable to modify the primary aerosolspray generated by a nebulization catheter. One way that this can beaccomplished is by causing the primary aerosol spray to impact upon abaffle placed in its path, the velocity and direction of the spray canbe altered and the size of the distribution of the aerosol can bemodified creating a secondary aerosol. Impaction upon a properly locatedbaffle can break up large aerosol particles creating a finer aerosolmist. The baffle also deflects or diffuses the airstream carrying theparticles reducing their forward velocity and altering their direction.This can lessen impaction on the carina or airways and enhance theentrainment of the particles into the inspiratory flow. Embodiments ofnebulizing catheters incorporating an impaction baffle to provide asecondary aerosol are shown in FIGS. 61-64.

Referring to FIG. 61, a nebulization catheter 1140 has a gas lumen 1142and a liquid lumen 1144 located in a shaft 1146 of the catheter. The gaslumen 1142 conveys a pressurized gas to a distal gas orifice 1148 andthe liquid lumen 1144 conveys liquid to a distal liquid orifice 1150. Abaffle 1152 connects to a baffle extension tube 1154 so that the baffle1152 is located distally of the liquid orifice 1150. The baffle 1152 ispreferably located as close to the solution orifice 1150 as possiblewithout interfering with the generation of the primary aerosol.

Some of the primary aerosol that is not broken into fine particles mayremain on the baffle 1152 and build up over time forming a thin liquidfilm on the surface of the baffle 1152. If this film is left to buildup, it will form droplets that either fall or are blown off the baffle.These droplets may become quite large and of little or no therapeuticvalue representing a waste of the solution.

In order to recirculate this film of solution, the baffle 1152 may beused to collect and return the liquid solution to a liquid supply lumen1144 To achieve this, the baffle may have with one or more orifices 1158or porous material on its surface of the baffle 1152 for the collectionof the film of solution. The orifices 1158 drain into or through thebaffle, and are in fluid communication with the solution supply lumen1144 via a lumen located inside of the extension tube 1154. The lumeninside the extension tube 1154 may communicate directly with thesolution lumen 1144 or extension thereof.

In the embodiment of FIG. 61, the negative pressure generated at thenebulization orifice 1150 by the gas flow over it is used to draw therecirculated solution from the baffle recirculation orifice 1158 via thelumen in the extension 1154 and out the liquid orifice 1150 again. Inthis case, the recirculation orifices 1158 or surface should be in anarea of higher ambient pressure than the solution orifice 1150 to causethe recirculation of the fluid. This may be accomplished by locating thecollection orifices 1158 on a distal side of the baffle 1152 oppositethe solution and gas orifices 1150 and 1148. The flow of new solution(from the proximally located solution reservoir) pumped into thesolution lumen 1144 should be less than the flow drawn from the solutionorifice 1150 to ensure that least some of the solution from the baffle1152 is recirculated to the orifice 1150.

FIG. 62 shows another embodiment of a nebulization catheter thatincorporates a baffle for the purpose of generating a secondary aerosol.This embodiment is similar to the nebulization catheter in FIG. 61 withthe exception that the recirculated fluid is drawn back into arecirculation lumen 1160 in the catheter shaft 1146. The recirculationlumen 1160 communicates with the liquid lumen 1144 at a junction 1162 atwhich location the recirculated solution is mixed with newly suppliedliquid in the solution lumen 1144.

FIG. 63 shows another alternative embodiment. This embodiment is similarto the embodiment of FIG. 62 except that the recirculated solution isrouted from the baffle 1152 to the recirculation lumen 1160 and then toa separate solution orifice for re-nebulization. This dedicated solutionorifice 1161 is also located at the catheter tip near a gas orifice 1148to produce nebulization. The aerosol generated from this separateorifice 1161 is directed into the common baffle 1158 to break it intosmaller particles and a portion of the solution will again remain on thebaffle and be recirculated. This approach can eliminate the difficultiesof balancing the flow of new and recirculated solution to a singlesolution orifice.

Referring to FIG. 64, there is another embodiment of a nebulizingcatheter incorporating a baffle for the generation of a secondaryaerosol. In this embodiment, a nebulizing catheter 1170 has a shaft 1172with a liquid lumen 1174 connected to a liquid supply 1176. A gas lumen1178 connects to a pressured gas source 1180. The liquid lumen 1174communicates with a distal liquid orifice 1182 and the gas lumencommunicates with a distal gas orifice 1184. A baffle 1186 is located infront of the liquid orifice 1182. Aerosol impacting on the baffle 1186produces a secondary aerosol that flows around the baffle 1186. Aresidue film of liquid migrates around the baffle 1186 and enters intobaffle orifices 1190 located on the distal side of the baffle 1186. Thebaffle orifices 1190 communicate with a recirculation lumen 1192 thatextends through the catheter shaft to a reservoir 1194 located outsideof the body where the recirculated solution is combined withnon-recirculated solution pumped from a proximal drug reservoir. Theflow of recirculated and non-recirculated solution into the systemshould be carefully balanced to match the amount of aerosol generated.To achieve this, flow metering and pumping strategies can be employed.

D. Nebulization Catheter with Pressurized Propellant-Drug Canister

In the embodiments described above, medicine is delivered in liquid formto the distal liquid orifice. In another embodiment, illustrated in thediagram of FIG. 65, the medicine may be mixed with a propellant andmaintained under pressure and delivered under pressure to the distal tipof a nebulizing catheter 1198. A pressured medicine-liquid propellantmixture could be supplied from a pressurized canister 1200 such as thoseused as a component of a metered or non-metered dose inhaler. By using apropellant, an aerosol could be generated from the distal end 1202 ofthe catheter even without the addition of the pressurized nebulizinggas. However, the delivery of pressurized gas 1204 from the distal endof the nebulization catheter would be used to assist in breaking up anylarger medicine particles and also assist dispersing the aerosolizeddrug solution delivered through the catheter as well as help shape theaerosol plume. For example, the delivery of the pressurized, nebulizinggas may assist in shielding the aerosol generated by the medicine-liquidpropellant mixture and help avoid losses due to impaction.

E. Nebulizing Function Incorporated in Suction Catheter

As mentioned above, the nebulizing catheter can be incorporated intoanother device, such as an endotracheal tube, either removably ornon-removably. Another such device into which a nebulizing catheter canbe adapted is a suction or aspiration catheter. A suction catheter issometimes used in conjunction with patients who are intubated. A suctioncatheter has an O.D. and a length such that it can be inserted throughthe ventilation lumen of an endotracheal tube. The suction catheter isused to aspirate fluids and mucin secretions that collect in therespiratory tract of in the endotracheal tube of a patient who isintubated. A conventional suction catheter is inserted down theventilation lumen of the endotracheal tube and out the distal end. Amucolytic agent may be instilled as a liquid via a lumen of the suctioncatheter to help in the withdrawal of mucin from the trachea or bronchi.The suction catheter may then be withdrawn from the endotracheal tubeand either disposed or retained in a sterile sheath connected to aproximal end of the endotracheal tube so that it can be reinserted intothe endotracheal tube again.

A nebulizing catheter can be incorporated into a suction catheter sothat a single device can perform both the functions of aspiration andnebulization for aerosol delivery. In an alternative embodiment of thepresent invention, the nebulizing catheter, such as described above,could be incorporated into a suction catheter so that a single cathetercan provide both functions. This could be accomplished by provided anyof the embodiments of the nebulization catheter described above with aseparate lumen for the purpose of providing a suction to withdraw fluidfrom a patient's respiratory tract. Combining the functions of a suctioncatheter and nebulization catheter into a single device has theadvantages of avoiding the expense of separate products as well asavoiding the inconvenience of inserting and withdrawing separatedevices.

Embodiments of a suction catheter combined with a nebulization catheterare shown catheter is FIGS. 66-73. FIGS. 66-70 show a suction catheterassembly 1220. The suction catheter assembly 1220 includes a suctioncatheter shaft 1222 slidably located inside of a flexible sheath 1224. Asuction lumen 1225 extends through the suction catheter shaft 1222. Aproximal manifold 1226 includes a port 1228 for connecting a vacuumsource to the suction catheter lumen 1225. A valve 1230 operates to openand close the port 1228. A distal sleeve 1232 provides for connecting toan endotracheal tube such that the suction catheter shaft 1222 can beinserted into the endotracheal tube by pushing the proximal manifold1226 toward the distal sleeve 1232. The distal sleeve 1232 may include amanifold for connection to a flush port 1233. A seal 1235 located in thesleeve 1232 closely bears on the suction catheter shaft to remove mucousor other unwanted materials that can be removed via the flush port 1233.The shaft of the suction catheter may be provided with a low friction,e.g. hydrophilic, coating to reduce adhesion of mucous.

The suction catheter assembly 1220 includes two additional lumens 1234and 1236. These lumens 1234 and 1236 are located in a wall of thesuction catheter shaft 1222. These lumens 1234 and 1236 communicate withdistal orifices 1238 and 1240 located at a distal end of the suctioncatheter shaft 1222. These lumens 1234 and 1236 are used to deliver aliquid medicine and a pressurized gas for nebulizing the liquidmedicine, as described above. Also located at a distal end of thesuction catheter shaft 1222 are suction openings 1242.

The suction catheter assembly 1220 can be used in a conventional mannerto remove mucin from the trachea and from the bronchi. The suctioncatheter assembly 1220 can also be used to deliver medicines to thelungs as an aerosol by means of the nebulizing lumens 1234 and 1236. Thenebulizing lumens can also be used to deliver mucolytic agents as anaerosol. Because the fine aerosol delivered by the nebulizing lumens canbe carried by a patient's inspiratory airflow into the bronchi, themucolytic agent can be delivered further into bronchi compared to asuction catheter that merely instills or generates a coarse spray of amucolytic agent. In addition, the flow velocity produced by the gaspressurization lumen may be used to assist in breaking up mucous at theend of the suction catheter.

When using the suction catheter assembly 1220, it can be positioned sothat a distal end of the suction catheter shaft 1222 is close to thedistal end of the endotracheal tube 1250 as shown in FIG. 68 oralternatively the suction catheter shaft 1222 can be positioned so thatit extends past the distal end of the endotracheal tube 1250 as shown inFIG. 70. As shown in FIG. 70, the suction catheter shaft 1220 may beformed with a distal curvature so that the distal end can be broughtinto proximity with the tracheal wall.

Rather than incorporate the nebulizing lumens into the wall of thesuction catheter, it may be preferably in many situations to use aconventional suction catheter with a stand-alone nebulizing catheter.The stand-alone nebulizing catheter may be similar to any of theembodiments described above. A suction catheter and a nebulizingcatheter can readily be used together with the alternative versions ofthe manifolds shown in FIGS. 71-73.

Referring to FIG. 71, an endotracheal tube 1252 has a proximal end witha single port 1254. A suction catheter 1256 has a distal manifold 1258.The distal manifold 1256 could be formed as part of the suction catheter1256 or could be provided as a separate component. The suction cathetermanifold 1258 connects to the single port 1254 of the endotracheal tube1252. The manifold 1258 has a first port 1260 for connecting to aventilator and a second port 1264 for connecting to a proximal end of anebulizing catheter 1266. As shown in FIG. 71, the nebulizing catheter1266 includes a sterile sheath 1268 which is similar to the sheathincluded on the suction catheter 1262. In the embodiment of FIG. 71, thesuction catheter 1256 and the nebulizing catheter 1266 are positionedalternately inside the ventilation lumen of the endotracheal tube 1252.The suction catheter or the nebulizing catheter can be withdrawntemporarily and maintained in its sterile sheath while the other isbeing used.

Referring to FIG. 72 there is another arrangement for connecting asuction catheter and nebulizing catheter to an endotracheal tube. Inthis embodiment, a manifold 1270 connects to the proximal end of theendotracheal tube 1252. The manifold 1270 has port 1274 for receivingthe nebulizing catheter 1266 and a second port 1276. A distal manifold1278 of a suction catheter 1280 connects to the second port 1276. Thesuction catheter manifold 1278 has a port 1282 for connecting to theventilator. This arrangement can be used similarly to the arrangement ofFIG. 71.

FIG. 73 shows still another arrangement for connecting a suctioncatheter and a nebulizing catheter to an endotracheal tube. In thisembodiment, the endotracheal tube 1252 is provided with a proximal endthat includes dual ports. A first port 1284 receives the nebulizingcatheter 1266. The second port 1286 may be connected to either directlyto a ventilator or may be connected to a distal end of a suctioncatheter (not shown) in a conventional manner.

In another alternative embodiment (not shown), the nebulizing cathetercould be positioned down the suction lumen of the suction catheter.

FIG. 74 shows another embodiment of a suction catheter alsoincorporating a nebulization of an aerosol. In FIG. 74, a suctioncatheter 1400 is extends from the ventilation lumen of an endotrachealtube 1250. The suction catheter 1400 includes distal suction orifices1402 located close to the distal end of the suction catheter shaft.Located along the suction catheter shaft proximally of the suctionorifices 1402 are one or more pairs of liquid and gas orifices 1404. Theliquid and gas orifice pairs 1404 are located with respect to each otherto produce an aerosol of the liquid being delivered to the liquidorifice as in the previous embodiments. The nebulization orifices 1404are oriented radially from the suction catheter shaft to direct theaerosol delivered from the nebulization orifices 1404 toward the airwaypassage wall. In one embodiment, the aerosol being delivered is amucolytic agent. The suction provided by the suction orifices draws themucolytic agent delivered from the nebulization orifices as well asmucous treated by the mucolytic agent in a distal direction into thesuction orifices 1402.

Another embodiment of the suction catheter with aerosol delivery isshown in FIG. 75. A suction catheter 1410 is located in a ventilationlumen of the endotracheal tube 1250. As in the previous embodiment, thesuction catheter 1410 has a distal suction orifice 1412 for removingmucous from the airway passage. In addition, the suction catheter 1410also includes distal gas and liquid orifices 1414 located in proximityto each other to produce a aerosol. The liquid and gas orifices arelocated in a distal extension 1416 of the suction catheter shaft so thatthey are distal of the suction orifice 1412. The liquid and gasnebulization orifices 1414 are oriented in a proximal direction towardthe suction orifice 1412. The distal extension 1416 is formed to bringthe nebulization orifices 1414 close to the wall of airway passage sothat the aerosol delivered from the nebulization orifices 1414 washesthe airway passage wall. As in the previous embodiment, the aerosoldelivered may be a mucolytic agent to facilitate suctioning of themucous out of the airway passage. The pressurized gas flow may be usedto contribute to the dislodgement of mucous from the airway passagewalls.

F. Nebulization with Vibration

A vibrating orifice, a screen with multiple orifices or perforations, ora vibrating wire located at the distal tip of the nebulizing cathetermay also be employed to assist in the generation of fine aerosolparticles. The vibration may be generated by electromechanical,hydraulic, pneumatic, or piezoelectric means. The vibrations may begenerated at the tip of the catheter, in the shaft, or extracorporeally.

One embodiment of a nebulizing catheter incorporating a vibrating tip isshown in FIG. 76. A nebulizing catheter 1300 includes a shaft 1302through which extend a lumen 1304 for the delivery of a liquid medicineand a lumen 1306 for the delivery of a pressurized gas. The liquid lumen1304 communicates with a distal liquid orifice 1308 and the gas lumen1306 communicates with a distal gas orifice 1310 located at a distal endof the nebulizing catheter shaft. At the tip the orifices 1308 and 1310may be drilled or formed in a piezoelectric material 1314 or may bedrilled or formed in an orifice insert, plate, tube or screenmechanically attached to the tip such that the vibrations of thematerial are transferred to orifices. Although both the gas and liquidorifices may be vibrated, alternatively only the liquid orifice may bevibrated. In still a further embodiment, the entire shaft of thecatheter may be vibrated so that the vibrations are transferred to thetip. The vibrations may be amplified by mechanical means to increase theamplitude of the orifice oscillation. Two electrical lead wires 1316 and1318 may be used to conduct bipolar or unipolar pulses from anextracorporeal generator and control circuit to the piezoelectricmaterial 1314. The amplitude and frequency of the orifice vibrations maybe adjusted to optimize aerosol production based on the gas and solutionflow rates, the orifice configuration, and the desired size of theaerosol particles. The generation device would be provided with acurrent leakage sensor to terminate its operation in the event itdetects current leakage in the system. The vibrations can be pulsed tocoincide with inspiration and also to control heat generated byvibration at the tip. One or more gas supply lumens and orifices at thecatheter tip can be used to assist in the dispersion and transport ofthe particles produced at the vibrating orifice.

In a further alternative embodiment, the orifice may be vibrated bymeans of a vibrating wire connected to the orifice that is caused tovibrate from a generator connected to the proximal end. In still afurther embodiment, a vibrating wire, similar to the wire tip shown inFIGS. 16-19, may extend distally past a non-vibrating orifice to causeaerosolization of a liquid delivered from the orifice that impinges ontothe vibrating wire. In a still further embodiment, the tip may bevibrated remotely, e.g. from a source outside the body, by means of amagnetic field.

A liquid supply to the catheter tip can also be rapidly pulsed to causesmall droplets to be ejected at the solution orifice. This may cause afiner aerosol to be developed than by feeding a continuous stream ofsolution to the orifice. The pulsation can be accomplished by rapidlyexpanding and contracting all or part of the solution reservoir(including the lumen). The expansion and contraction of the reservoircan be caused by electromechanical, hydraulic, pneumatic, orpiezoelectric actuators forming the reservoir, within the reservoir ormoving flexible portions of the reservoir. Such an embodiment is shownin FIG. 76. A nebulizing catheter 1500 includes a shaft 1502 having agas lumen 1502 connected to a source of pressurized gas 1504 and aliquid medicine lumen 1506 connected to a source of liquid medicine1508. Included in the liquid medicine source 1508 is a means forimparting compression waves or pulsation into the liquid. The waves areindicated in the liquid at 1509. The wave imparting means may be atransducer 1510 or other similar device. The vibration inducing device1510 may be driven by a frequency generator 1513 at a frequency greaterthan 100 hertz. The vibrations induced in the liquid may be focussed ordirected toward the distal liquid orifice 1514.

In the case where the vibrations are generated at a location proximal ofthe tip, the nebulizing catheter shaft may incorporate a mechanicalmeans in the shaft or near the orifices capable of transmitting oramplifying the pulsations. In the embodiment of FIG. 77, a wire 1516 mayextend from the pulsation generating means 1510 into the liquid lumen1506 to help convey the vibrations 1509 to the distal orifice 1514. Thepulsations imparted to the liquid may be used to generate an aerosolfrom the distal liquid orifice 1514 or alternatively may be used inconjunction with the pressurized gas delivered through the gas lumen1502 for enhanced aerosolization. The amplitude and frequency of theorifice vibrations may be adjusted to optimize aerosol production basedon the gas and solution flow rates, the orifice configuration, and thedesired size of the aerosol particles.

The volume dispersed from the liquid orifice 1514 by each pulse shouldbe less than approximately 10 microliters and the pulsation should occurat a frequency greater than 100 Hertz, although smaller volumes andfaster frequencies may be used to produce a finer aerosol. It ispreferable that the reservoir and lumens be constructed or a material ofminimal compliance to ensure minimal attenuation of the pulsation. Thegas supply orifice at the catheter tip can be used to assist in thedispersion and transport of the particles produced at the solutionorifice. These micro pulsations can be incorporated into a series withpauses between them to coincide with the patient's inspiratory phase.

G. Other Method for Aerosol Generation

The above embodiments describe a nebulization catheter in which anaerosol is generated by directing a pressurized gas through a catheternear an orifice from which the liquid to be nebulized exits. It isconsidered to be within the scope of the invention described herein touse other means or agents to generate an aerosol for delivery of amedication to the respiratory tract. For example, the above embodimentsmay be used in conjunction with devices that utilize other means togenerate an aerosol of a liquid medication. A liquid delivered by asingle liquid lumen may be nebulized by applying ultrasonic energy tothe liquid, electrospray, steam, or a micropump similar to those used inink jet type printers. These alternative approaches to nebulization maybe substituted for the use of a pressurized gas for some of theembodiments described above, or may be combined with pressurized gas orwith each other to produce an aerosol of the liquid medication.

The nebulization catheter embodiments described herein could also beused in other types of nebulizers that are used externally of apatient's respiratory system, such as small volume nebulizers (SVN),humidification nebulizers, or nebulizers used for ocular or nasal drugadministration. When used in such other types of nebulizers, theembodiments of the nebulization catheter disclosed herein provide for afine aerosol without the potential disadvantages of impacting the liquidon a baffle or recirculating the liquid medicine on a continuous basiswhich are common in such nebulizers.

It is intended that the foregoing detailed description be regarded asillustrative rather than limiting and that it is understood that thefollowing claims including all equivalents are intended to define thescope of the invention.

I claim:
 1. A method for delivering a medicine to a patient'srespiratory system, comprising:positioning an endotracheal tube in thepatient's respiratory system; positioning a standalone nebulizationcatheter, said standalone nebulization catheter being separate from saidendotracheal tube in the patient's respiratory system and receiving anindication of the position of the nebulization catheter relative to theendotracheal tube; operating the nebulization catheter to produce anaerosol of the medicine at a distal end of the nebulization catheterwhile the endotracheal tube is positioned in the patient's respiratorysystem; delivering a liquid medicine to a first orifice located at thedistal end of the nebulization catheter; and delivering a pressurizedgas to a second orifice located at the distal end of the nebulizationcatheter in proximity to the first orifice to aerosolize the liquidmedicine at the first orifice.
 2. The method of claim 1 furthercomprising:centering the nebulization catheter in the endotracheal tube.3. The method of claim 1 in which the step of positioning a nebulizationcatheter further comprises:positioning a nebulization catheter throughan auxiliary lumen of the endotracheal tube.
 4. The method of claim 1further comprising:removing the nebulization catheter while leaving theendotracheal tube in position in the patient's respiratory system. 5.The method of claim 1 further comprising:providing a coaxial airflow tosaid distal end of said nebulization catheter to constrain aerosoltherefrom.
 6. The method of claim 1 further comprising:providinghumidification to the patient's respiratory system.
 7. The method ofclaim 1 in which the indication is a tactile indication.
 8. The methodof claim 1 in which the step of receiving an indication furthercomprises:receiving an indication of pressure variation at a distal endof the endotracheal tube as the distal end of the nebulization catheteris moved past.
 9. The method of claim 1 in which the nebulizationcatheter is positioned in a patient who has a tracheotomy.
 10. Themethod of claim 1 in which the nebulization catheter is positioned via atracheotomy tube.
 11. The method of claim 1 in which production of theaerosol at the distal end of the nebulization catheter is synchronizedwith inhalation of the patient.
 12. The method of claim 11 furthercomprising the step of:pulsing delivery of liquid.
 13. The method ofclaim 12 further comprising the step of:pulsing delivery of gas.
 14. Themethod of claim 11 further comprising the step of:pulsing delivery ofgas.
 15. The method of claim 11 in which production of the aerosol isbegun in advance of the inhalation of the patient.
 16. The method ofclaim 1 further comprising the steps of:sensing a physiologicalcondition of the patient, and operating the nebulization catheter toproduce the aerosol as a function of the condition sensed.
 17. A methodfor delivering a medicine to a patient's respiratory system,comprising:positioning an endotracheal tube in the patient's respiratorysystem; positioning a standalone nebulization catheter, said standalonenebulization catheter being separate from said endotracheal tube in thepatient's respiratory system; operating the nebulization catheter toproduce an aerosol of the medicine at a distal end of the nebulizationcatheter while the endotracheal tube is positioned in the patient'srespiratory system; connecting a pressurized canister containing amixture of a medicine and a liquid propellant to a proximal end of thenebulization catheter; delivering the mixture of medicine and liquidpropellant through a first lumen of the nebulization catheter to a firstdistal orifice located at the distal end of the nebulization catheter;and delivering a pressurized gas through a second lumen of thenebulization catheter to a second orifice located at the distal end ofthe nebulization catheter in proximity to the first orifice to enhancethe aerosolization of the medicine emitted from the first orifice. 18.The method of claim 17 in which the pressurized gas from the secondorifice is directed opposite the medicine and propellant delivered fromthe first distal orifice.
 19. A method for delivering a medicine to apatient's respiratory system, comprising:positioning an endotrachealtube in the patient's respiratory system, positioning a standalonenebulization catheter, said standalone nebulization catheter beingseparate from said endotracheal tube in the patient's respiratorysystem; operating the nebulization catheter to produce an aerosol of themedicine at a distal end of the nebulization catheter while theendotracheal tube is positioned in the patient's respiratory system; andapplying an electric signal to the distal end of the nebulizationcatheter to produce the aerosol from said distal end.
 20. The inventionof claim 19 wherein the electric signal applied to the distal end of thenebulization catheter causes a vibration that produces the aerosol. 21.The invention of claim 19 wherein the electric signal applied to thedistal end of the nebulization catheter is applied to a piezoelectricmaterial.
 22. The invention of claim 19 wherein the electric signal isapplied to produce an aerosol by ultrasonic vibration.
 23. The inventionof claim 19 wherein the electric signal is applied to produce an aerosolby electrospray.
 24. The invention of claim 19 wherein the electricsignal is applied to produce an aerosol from a single lumen of thecatheter.
 25. A method for delivering a medicine to a patient'srespiratory system, comprising:positioning an endotracheal tube in thepatient's respiratory system; positioning a standalone nebulizationcatheter, said standalone nebulization catheter being separate from saidendotracheal tube in the patient's respiratory system; operating thenebulization catheter to produce an aerosol of the medicine at a distalend of the nebulization catheter while the endotracheal tube ispositioned in the patient's respiratory system; delivering a liquidmedicine to a first orifice located at the distal end of thenebulization catheter; delivering a pressurized gas to a second orificelocated at the distal end of the nebulization catheter in proximity tothe orifice to aerosolize the liquid medicine at the first orifice; andbalancing airflow at the distal end of the nebulization catheter bywithdrawing air through a vacuum lumen extending through thenebulization catheter.
 26. The method of claim 25 further comprising thestep of:positioning the nebulization catheter in a working channel of abronchoscope.
 27. A method for delivering a medicine to one or bothlungs of a patient who is not intubated with an endotracheal tube,comprising:positioning a nebulization catheter in the patient'srespiratory system; positioning the nebulization catheter in a channelof bronchoscope; operating the nebulization catheter to produce anaerosol of the medicine at a distal end of the nebulization catheter;delivering a liquid medicine to a first orifice located at the distalend of the nebulization catheter; and delivering a pressurized gas to asecond orifice located at the distal end of the nebulization catheter inproximity to the orifice to aerosolize the liquid medicine at the firstorifice.
 28. A method of delivering an aerosol of medication to apatient's lungs, comprising:nebulizing the medication at a distal end ofa catheter located in the patient's respiratory tract, said distal endof said catheter directed in a first direction; and directing a flow ofgas at said nebulized medication in a direction opposite to said firstdirection.
 29. The method of claim 28 in which said first direction insaid nebulizing step is a distal direction.
 30. The method of claim 28in which said first direction in said nebulizing step is a proximaldirection.
 31. The method of claim 28 in which said directing step isfurther characterized by:directing a flow of gas from a distal end of anendotracheal tube.
 32. The method of claim 28 in which said flow of gasis an inhalation of the patient through an endotracheal tube.
 33. Amethod of delivering a medicine selectively to a bifurcated region of apatient's respiratory system, comprising:positioning a catheter into abranch of the patient's respiratory system that leads to a region otherthan the region to which the medicine is to be delivered; delivering anairflow through the catheter; and nebulizing the medicine in therespiratory system proximal of where the airflow is delivered whereby aplume of the nebulized medicine is delivered to the region without thecatheter.
 34. A method for delivering a medicine to a patient'srespiratory system, comprising:positioning an endotracheal tube in thepatient's respiratory system; positioning a standalone nebulizationcatheter, said standalone nebulization catheter being separate from saidendotracheal tube in the patient's respiratory system; operating thenebulization catheter to produce an aerosol of the medicine at a distalend of the nebulization cater while the endotracheal tube is positionedin the patient's respiratory system; delivering a liquid medicine to afirst orifice located at the distal end of the nebulization catheter;delivering a pressurized gas to a second orifice located at the distalend of the nebulization catheter in proximity to the first orifice toaerosolize the liquid medicine at the first orifice; and wherein theaerosol is produced by vibrating a distal orifice of the nebulizingcatheter.
 35. The invention of claim 34 wherein the vibrating isproduced by a mechanical means in a shaft of the nebulzation catheter.36. The invention of claim 34 wherein the vibrating is produced by amechanical means near the distal orifice of the nebulzation catheter.